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Molecular Differences in Sporadic Breast Cancer in Young Women (≤ 35-Year Old): Analysis of TGFBI, DDB2 and MCM5

By Dona Touma

Abstract

The aim of this study was to investigate mRNA and protein expression of three genes (Transforming Growth Factor Beta Induced (TGFBI), Damaged-Specific DNA Binding (DDB2) and Minichromosomal Maintenance-5 (MCM5)) in breast cancers. Q-RT-PCR (36 cancers, 8 normal/benign tissues and 9 organoid samples), western blotting (6 cell lines, 6 cancers and 4 normal/benign tissues) and immunohistochemistry (67 breast cancers) were performed, and for TGFBI functional assays (viability, apoptosis and invasion) were carried out in two cell lines (ZR-75-1 and MDA-MB-468) after transient transfection with recombinant TGFBI and vector controls. \ud TGFBI showed reduced mRNA and protein expression in all cancer cell lines relative to HBL-100. The mRNA levels were also significantly lower in breast cancers compared to normal/benign tissues. Immunohistochemistry results showed that 46 / 67 breast cancers were negative or had <1% nuclear staining. There was a significant correlation between TGFBI mRNA levels and patient age; with lower levels expressed in younger women (p=0.04). Higher expression of DDB2 mRNA was observed in ER/PR positive (MCF-7, T47-D and ZR-75-1) compared to ER/PR negative (HBL-100, MDA-MB-231 and MDA-MB-468) cell lines. Higher DDB2 mRNA levels was significantly correlated with ER positive (p=0.04) and grade II (p=0.02) tumours; lower levels were associated with younger patient age (p=0.025). In addition, higher DDB2 protein expression was associated with ER (p=0.001) and PR (p=0.004). Elevated MCM5 mRNA and protein levels were observed in MCF-7 and MDA-MB-231. MCM5 immunoreactivity was significantly correlated with low grade (p=0.02) and ER/PR positive (ER p=0.04 and PR p=0.01) tumours. Transfection with TGFBI had no effect on viability, apoptosis and invasion of ZR-75-1 and MDA-MB-468 cells. \ud In conclusion, the results fail to support the hypothesis of this study, namely that expression of TGFBI, DDB2 and MCM5 could contribute to the more aggressive features of sporadic breast cancers in younger women

Publisher: University of Leicester
Year: 2011
OAI identifier: oai:lra.le.ac.uk:2381/9164

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  1. (2006). 17-Beta-estradiol induces transformation and tumorigenesis in human breast epithelial cells&quot;, The FASEB journal : official publication of the Federation of American Societies for Experimental Biology,
  2. (2008). A candidate molecular signature associated with tamoxifen failure in primary breast cancer&quot;,
  3. (1982). A cell line (HBL-100) established from human breast milk&quot;,
  4. (2002). A gene-expression signature as a predictor of survival in breast cancer&quot;, The New England journal of medicine,
  5. (2007). A genome-wide association study identifies alleles in FGFR2 associated with risk of sporadic postmenopausal breast cancer&quot;,
  6. (2004). A multigene assay to predict recurrence of tamoxifen-treated, node-negative breast cancer&quot;, The New England journal of medicine,
  7. (2008). A prospective study of age-specific physical activity and premenopausal breast cancer&quot;,
  8. (2009). A protein-based set of reference markers for liver tissues and hepatocellular carcinoma&quot;,
  9. (1976). A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding&quot;,
  10. (2004). A Ser49Cys variant in the ataxia telangiectasia, mutated, gene that is more common in patients with breast carcinoma compared with population controls&quot;,
  11. (2000). A TGF-beta-inducible cell adhesion molecule, betaig-h3, is downregulated in melorheostosis and involved in osteogenesis&quot;,
  12. (2004). A two-gene expression ratio predicts clinical outcome in breast cancer patients treated with tamoxifen&quot;,
  13. (2000). Absolute quantification of mRNA using real-time reverse transcription polymerase chain reaction assays&quot;,
  14. (2006). AceView: a comprehensive cDNA-supported gene and transcripts annotation&quot;,
  15. (2003). Advantages and limitations of microarray technology in human cancer&quot;,
  16. (1993). Age as prognostic factor in premenopausal breast carcinoma&quot;,
  17. (2007). Alcohol intake and breast cancer risk: the European Prospective Investigation into Cancer and Nutrition (EPIC)&quot;,
  18. (2008). Allele-specific up-regulation of FGFR2 increases susceptibility to breast cancer&quot;,
  19. (1975). An atlas of subgross pathology of the human breast with special reference to possible precancerous lesions&quot;,
  20. (2008). An overview of prognostic factors for long-term survivors of breast cancer&quot;, Breast cancer research and treatment,
  21. (1998). Analogs of staurosporine: potential anticancer drugs?&quot;,
  22. (2008). Annotating breast cancer microarray samples using ontologies&quot;,
  23. (2001). Antigen retrieval techniques: current perspectives&quot;, The journal of histochemistry and cytochemistry :
  24. (2008). Are the so-called low penetrance breast cancer genes, ATM, BRIP1, PALB2 and CHEK2, high risk for women with strong family histories?&quot;,
  25. (2008). Aspirin use and breast cancer risk: a meta-analysis and meta-regression of observational studies from
  26. (2010). Association of invasion-promoting tenascin-C additional domains with breast cancers in young women&quot;,
  27. (1991). Ataxiatelangiectasia: an interdisciplinary approach to pathogenesis&quot;,
  28. (2003). Average risks of breast and ovarian cancer associated with BRCA1 or BRCA2 mutations detected in case Series unselected for family history: a combined analysis of 22 studies&quot;,
  29. (2003). Basal transcriptional regulation of human damage-specific DNA-binding protein genes
  30. (2008). Basal-like breast cancer: a critical review&quot;,
  31. (2005). Benign breast disease and the risk of breast cancer&quot;, The New England journal of medicine,
  32. (2004). Beta ig-h3 promotes renal proximal tubular epithelial cell adhesion, migration and proliferation through the interaction with alpha3beta1 integrin&quot;,
  33. (1995). Beta IG-H3, a novel secretory protein inducible by transforming growth factor-beta, is present in normal skin and promotes the adhesion and spreading of dermal fibroblasts in vitro&quot;,
  34. (1994). beta ig-h3: a transforming growth factor-beta-responsive gene encoding a secreted protein that inhibits cell attachment in vitro and suppresses the growth of CHO cells in nude mice&quot;, DNA and cell biology,
  35. (1997). Beta-ig. Molecular cloning and in situ hybridization in corneal tissues&quot;,
  36. (2008). BigH3 protein expression as a marker for breast cancer&quot;,
  37. (2005). Biology of progesterone receptor loss in breast cancer and its implications for endocrine therapy&quot;,
  38. (2000). Biopsy confirmed benign breast disease, postmenopausal use of exogenous female hormones, and breast carcinoma risk&quot;,
  39. (1996). Blocking of glioma proliferation in vitro and in vivo and potentiating the effects of BCNU and cisplatin: UCN-01, a selective protein kinase C inhibitor&quot;,
  40. (2006). BRCA1, BRCA2 and TP53 mutations in very early-onset breast cancer with associated risks to relatives&quot;, European journal of cancer
  41. (1997). Breast cancer and hormone replacement therapy: collaborative reanalysis of data from 51 epidemiological studies of 52,705 women with breast cancer and 108,411 women without breast cancer. Collaborative Group on Hormonal Factors in Breast Cancer&quot;,
  42. (2008). Breast cancer and use of nonsteroidal anti-inflammatory drugs: a meta-analysis&quot;,
  43. (2005). Breast cancer molecular subtypes respond differently to preoperative chemotherapy&quot;, Clinical cancer research : an official journal of the American Association for Cancer Research,
  44. (2010). Breast cancer precursors revisited: molecular features and progression pathways&quot;,
  45. (2000). Breast cancer prevention: a review of current evidence&quot;, CA: a cancer journal for clinicians,
  46. (1993). Breast cancer risk associated with proliferative breast disease and atypical hyperplasia&quot;,
  47. (2006). Breast cancer staging: working with the sixth edition of the AJCC Cancer Staging Manual&quot;, CA: a cancer journal for clinicians,
  48. (1998). Breast cancer susceptibility genes. BRCA1 and BRCA2&quot;,
  49. (2009). Breast cancer susceptibility: current knowledge and implications for genetic counselling&quot;,
  50. (2001). Breast cancer: hormones and other risk factors&quot;,
  51. (2007). Breast cancer: origins and evolution&quot;,
  52. (2010). Breast carcinoma cells re-express E-cadherin during mesenchymal to epithelial reverting transition&quot;,
  53. (1996). Breast carcinomas occurring in young women (< 35 years) are different&quot;,
  54. (2003). Breast cell invasive potential relates to the myoepithelial phenotype&quot;,
  55. (1998). Breast radiotherapy after breast-conserving surgery. The Steering Committee on Clinical Practice Guidelines for the Care and Treatment of Breast Cancer. Canadian Association of Radiation Oncologists&quot;,
  56. (2006). Breast-conserving surgery in early-stage breast cancer (indications, local recurrences, survival, cosmetic results)&quot;,
  57. (2009). C-terminal fragment of transforming growth factor beta-induced protein (TGFBIp) is required for apoptosis in human osteosarcoma cells&quot;,
  58. (2010). Cancer prevalence in 129 breast-ovarian cancer families tested for BRCA1 and BRCA2 mutations&quot;,
  59. (2002). Cancer Trialists' Collaborative Group
  60. (2005). Cancer Trialists' Collaborative Group (EBCTCG)
  61. (2007). Caspase expression profile and functional activity in a panel of breast cancer cell lines&quot;,
  62. (1992). cDNA cloning and sequence analysis of beta ig-h3, a novel gene induced in a human adenocarcinoma cell line after treatment with transforming growth factor-beta&quot;, DNA and cell biology,
  63. (1999). Cell growth-regulated expression of mammalian MCM5 and MCM6 genes mediated by the transcription factor E2F&quot;,
  64. (2010). Cell mechanics and the cytoskeleton&quot;,
  65. (2004). Cell-cycle checkpoints and cancer&quot;,
  66. (2005). Cell-cycle-dependent regulation of DNA replication and its relevance to cancer pathology&quot;,
  67. (2003). Challenges in the endocrine management of breast cancer&quot;,
  68. (2009). Characteristics and prognosis of breast cancer in younger women&quot;,
  69. (1997). Characterization of a cartilage-derived 66-kDa protein (RGD-CAP/beta ig-h3) that binds to collagen&quot;, Biochimica et biophysica acta,
  70. (1999). Characterization of DNA recognition by the human UV-damaged DNA-binding protein&quot;,
  71. (2007). CHK2 kinase: cancer susceptibility and cancer therapy - two sides of the same coin?&quot;,
  72. (1995). Chromosomal localization and cDNA cloning of the genes (DDB1 and DDB2) for the p127 and p48 subunits of a human damage-specific DNA binding protein&quot;,
  73. (1970). Cleavage of structural proteins during the assembly of the head of bacteriophage T4&quot;,
  74. (1976). Clinical staging of cancer of the head and neck: a new &quot;new&quot; system&quot;,
  75. (1993). Cloning of the rat progesterone receptor gene 5'-region and identification of two functionally distinct promoters&quot;,
  76. (2006). Co-expression of steroid receptors (estrogen receptor alpha and/or progesterone receptors) and Her-2/neu: Clinical implications&quot;, The Journal of steroid biochemistry and molecular biology,
  77. (1996). Coding sequence and chromosome mapping of the human gene (CDC46) for replication protein hCdc46/Mcm5&quot;, Cytogenetics and cell genetics,
  78. (2002). Collaborative Group on Hormonal Factors in Breast Cancer
  79. (2008). Commercialized multigene predictors of clinical outcome for breast cancer&quot;,
  80. (1998). Communication between the cell membrane and the nucleus: role of protein compartmentalization&quot;,
  81. (1999). Comparative genomic hybridization of breast tumors stratified by histological grade reveals new insights into the biological progression of breast cancer&quot;,
  82. (1993). Complementary distributions of vinculin and dystrophin define two distinct sarcolemma domains in smooth muscle&quot;,
  83. (2007). Concordant epigenetic silencing of transforming growth factor-beta signaling pathway genes occurs early in breast carcinogenesis&quot;,
  84. (1993). Conditional transformation of cells and rapid activation of the mitogen-activated protein kinase cascade by an estradiol-dependent human raf-1 protein kinase&quot;, Molecular and cellular biology,
  85. (1985). Conservative surgery and irradiation in the treatment of early breast cancer&quot;,
  86. (2006). Contributions of estrogen to ER-negative breast tumor growth&quot;, The Journal of steroid biochemistry and molecular biology,
  87. (2003). Covalent and non-covalent interactions of betaig-h3 with collagen VI. Beta ig-h3 is covalently attached to the amino-terminal region of collagen VI in tissue microfibrils&quot;,
  88. (2004). Cross-talk between estrogen receptor and growth factor pathways as a molecular target for overcoming endocrine resistance&quot;,
  89. (2002). Current surgical management of breast cancer&quot;,
  90. (2008). Damaged DNA binding protein 2 plays a role in breast cancer cell growth&quot;,
  91. (2002). DDB accumulates at DNA damage sites immediately after UV irradiation and directly stimulates nucleotide excision repair&quot;,
  92. (2003). DDB complexities&quot;,
  93. (2004). DDB2 gene disruption leads to skin tumors and resistance to apoptosis after exposure to ultraviolet light but not a chemical carcinogen&quot;,
  94. (2007). Ddb2 is a haploinsufficient tumor suppressor and controls spontaneous germ cell apoptosis&quot;, Human molecular genetics,
  95. (2010). De-regulated FGF receptors as therapeutic targets in cancer&quot;,
  96. (2001). Death receptor recruitment of endogenous caspase-10 and apoptosis initiation in the absence of caspase-8&quot;,
  97. (2007). Development and clinical utility of a 21-gene recurrence score prognostic assay in patients with early breast cancer treated with tamoxifen&quot;,
  98. (2003). Developmental expression patterns of Beta-ig (betaIG-H3) and its function as a cell adhesion protein&quot;,
  99. (2002). Diagnosis of genito-urinary tract cancer by detection of minichromosome maintenance 5 protein in urine sediments&quot;,
  100. (2004). Diagnosis of oesophageal cancer by detection of minichromosome maintenance 5 protein in gastric aspirates&quot;,
  101. (1993). Diet and carcinogenesis&quot;,
  102. (2003). Dietary fat and breast cancer risk revisited: a meta-analysis of the published literature&quot;,
  103. (2004). Differential expression of TGFbeta isoforms during differentiation of HaCaT human keratinocyte cells: implication for the separate role in epidermal differentiation&quot;,
  104. (2008). Distinct genomic aberration patterns are found in familial breast cancer associated with different immunohistochemical subtypes&quot;,
  105. (2010). DNA demethylating agents and epigenetic therapy of cancer&quot;,
  106. (2003). Do young breast cancer patients have worse outcomes?&quot;,
  107. (2002). Downregulation of Betaig-h3 gene is causally linked to tumorigenic phenotype in asbestos treated immortalized human bronchial epithelial cells&quot;,
  108. (2000). Ductal carcinoma in situ (DCIS) of the breast: evolving perspectives&quot;, Cancer treatment reviews,
  109. (1998). Ductal Carcinoma In Situ of the Breast: Controversial Issues&quot;,
  110. (1994). E-cadherin gene mutations provide clues to diffuse type gastric carcinomas&quot;,
  111. (2007). E2F regulates DDB2: consequences for DNA repair in Rb-deficient cells&quot;,
  112. (2009). Early primary breast cancer in the elderly - Pattern of presentation and treatment&quot;, Surgical oncology,
  113. (2000). Effect of hormone replacement therapy on breast cancer risk: estrogen versus estrogen plus progestin&quot;,
  114. (2002). Effects of cigarette smoke on the immune system&quot;,
  115. (2007). EGFR and Src are involved in indole-3-carbinol-induced death and cell cycle arrest of human breast cancer cells&quot;,
  116. (1992). Electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets: procedure and some applications.
  117. (2009). Elevated breast cancer mortality in women younger than age 40 years compared with older women is attributed to poorer survival in early-stage disease&quot;,
  118. (2005). Enhanced DDB2 expression protects mice from carcinogenic effects of chronic UV-B irradiation&quot;,
  119. (2003). Epigenetic and genetic alterations of APC and CDH1 genes in lobular breast cancer: relationships with abnormal E-cadherin and catenin expression and microsatellite instability&quot;,
  120. (2006). Epigenetic inactivation of Betaig-h3 gene in human cancer cells&quot;,
  121. (2006). Epigenetic silencing and deletion of the BRCA1 gene in sporadic breast cancer&quot;,
  122. (2006). Established breast cancer risk factors by clinically important tumour characteristics&quot;,
  123. (1979). Establishment and characterization of a cell line of human breast carcinoma origin&quot;,
  124. (1978). Establishment and characterization of three new continuous cell lines derived from human breast carcinomas&quot;,
  125. (1985). Estrogen receptor analyses. Correlation of biochemical and immunohistochemical methods using monoclonal antireceptor antibodies&quot;,
  126. (2000). Estrogen receptor beta is coexpressed with ERalpha and PR and associated with nodal status, grade, and proliferation rate in breast cancer&quot;, The American journal of pathology,
  127. (1973). Estrogen receptor in a human cell line (MCF7) from breast carcinoma&quot;,
  128. (1999). Estrogen receptor status by immunohistochemistry is superior to the ligand-binding assay for predicting response to adjuvant endocrine therapy in breast cancer&quot;,
  129. (1998). Evaluating atomic models of F-actin with an undecagold-tagged phalloidin derivative&quot;,
  130. (2005). Evaluation of housekeeping genes in placental comparative expression studies&quot;,
  131. (2003). Exploration of global gene expression patterns in pancreatic adenocarcinoma using cDNA microarrays&quot;, The American journal of pathology,
  132. (1995). Expression and ligand binding of alpha 2 beta 1 integrin on breast carcinoma cells&quot;,
  133. (2000). Expression of betaig-h3 by human bronchial smooth muscle cells: localization To the extracellular matrix and nucleus&quot;, American journal of respiratory cell and molecular biology,
  134. (1999). Expression of c-erbB4/HER4 is regulated in T47D breast carcinoma cells by retinoids and vitamin D3&quot;, Biochemical and biophysical research communications,
  135. (2002). Expression of cytokeratins 17 and 5 identifies a group of breast carcinomas with poor clinical outcome&quot;, The American journal of pathology,
  136. (1999). Expression of the p48 xeroderma pigmentosum gene is p53-dependent and is involved in global genomic repair&quot;,
  137. (1999). Expression profile of agonistic Smads in human breast cancer cells: absence of regulation by estrogens&quot;,
  138. (2000). Extracellular matrix and nuclear localization of beta ig-h3 in human bladder smooth muscle and fibroblast cells&quot;,
  139. (2008). Extracellular matrix protein betaigh3/TGFBI promotes metastasis of colon cancer by enhancing cell extravasation&quot;,
  140. (1990). Factors influencing survival and prognosis in early breast carcinoma (T1N0M0-T1N1M0). Assessment of 644 patients with median follow-up of 18 years&quot;,
  141. (2008). Factors predictive of response to hormone therapy in breast cancer&quot;,
  142. (2006). Fibroblasts in cancer&quot;,
  143. (2005). for Breast Screening Pathology. Pathology Reporting of Breast Disease. NHSBSP Publication No 58. Sheffield: NHS Cancer Screening Programmes and The Royal Collage of Pathologists,
  144. (2003). Forward mandibular positioning up-regulates SOX9 and type II collagen expression in the glenoid fossa&quot;,
  145. (2004). FuGENE 6 Transfection Reagent: the gentle power&quot;,
  146. (2003). G1 tetraploidy checkpoint and the suppression of tumorigenesis&quot;,
  147. (2006). Gene expression analysis by cDNA microarray in oral squamous cell carcinoma&quot;,
  148. (2006). Gene expression and benefit of chemotherapy in women with node-negative, estrogen receptor-positive breast cancer&quot;,
  149. (2001). Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications&quot;,
  150. (2002). Gene expression profiling predicts clinical outcome of breast cancer&quot;,
  151. (2005). Gene-expression profiles to predict distant metastasis of lymphnode-negative primary breast cancer&quot;,
  152. (2002). Genes other than BRCA1 and BRCA2 involved in breast cancer susceptibility&quot;,
  153. (1988). Genetic alterations during colorectal-tumor development&quot;, The New England journal of medicine,
  154. (1999). Genetic analysis of BRCA1 function in a defined tumor cell line&quot;,
  155. (2010). Genetic susceptibility to breast cancer&quot;,
  156. (2007). Genome-wide association study identifies novel breast cancer susceptibility loci&quot;,
  157. (1997). Germline mutations of the PTEN gene in Cowden disease, an inherited breast and thyroid cancer syndrome&quot;,
  158. (2001). Handbook Immunohistochemistry Staining Method”. Third Edition.
  159. (2001). HER2 as a prognostic factor in breast cancer&quot;,
  160. (2008). Hereditary breast cancer: new genetic developments, new therapeutic avenues&quot;,
  161. (1999). Heterozygous germ line hCHK2 mutations in LiFraumeni syndrome&quot;,
  162. (2010). High content analysis of histone acetylation in human cells and tissues&quot;,
  163. (2007). High frequency of coexistence of columnar cell lesions, lobular neoplasia, and low grade ductal carcinoma in situ with invasive tubular carcinoma and invasive lobular carcinoma&quot;,
  164. (2000). High incidence of breast and endometrial neoplasia resembling human Cowden syndrome in pten+/- mice&quot;,
  165. (1957). Histological grading and prognosis in breast cancer; a study of 1409 cases of which 359 have been followed for 15 years&quot;,
  166. (1990). Hormonal regulation of glucose transport in rat adipose cells&quot;,
  167. (2004). Human DDB2 splicing variants are dominant negative inhibitors of UV-damaged DNA repair&quot;, Biochemical and biophysical research communications,
  168. (1997). Identification of a candidate tumour suppressor gene, MMAC1, at chromosome 10q23.3 that is mutated in multiple advanced cancers&quot;,
  169. (2007). Identification of conserved gene expression features between murine mammary carcinoma models and human breast tumors&quot;,
  170. (2009). Identification of DDB2 protein as a transcriptional regulator of constitutive SOD2 gene expression in human breast cancer cells&quot;,
  171. (2001). Identification of gene expression profiles that predict the aggressive behavior of breast cancer cells&quot;,
  172. (2005). Identification of molecular apocrine breast tumours by microarray analysis&quot;,
  173. (2000). Identification of motifs for cell adhesion within the repeated domains of transforming growth factorbeta-induced gene, betaig-h3&quot;,
  174. (2002). Identification of motifs in the fasciclin domains of the transforming growth factorbeta-induced matrix protein betaig-h3 that interact with the alphavbeta5 integrin&quot;,
  175. (2009). Identification of proteins involved in neural progenitor cell targeting of gliomas&quot;,
  176. (2004). Immunohistochemical and clinical characterization of the basal-like subtype of invasive breast carcinoma&quot;, Clinical cancer research : an official journal of the American Association for Cancer Research,
  177. (1996). Immunohistochemical determination of oestrogen receptor: comparison of different methods of assessment of staining and correlation with clinical outcome of breast cancer patients&quot;,
  178. (1979). Immunoperoxidase technics in diagnostic pathology. Report of a workshop sponsored by the National Cancer Institute&quot;,
  179. (2008). Improved screening for anal neoplasia by immunocytochemical
  180. (2002). Induction and expression of betaig-h3 in pancreatic cancer cells&quot;,
  181. (2003). Induction of apoptosis in human corneal and HeLa cells by mutated BIGH3&quot;,
  182. (2002). Insulin-like growth factor binding proteins 1 and 3 and breast cancer outcomes&quot;, Breast cancer research and treatment,
  183. (2009). Integrated gene expression profile predicts prognosis of breast cancer patients&quot;, Breast cancer research and treatment,
  184. (2001). International Gastric Cancer Linkage Consortium
  185. (2007). Intrauterine factors and risk of breast cancer: a systematic review and meta-analysis of current evidence&quot;,
  186. (2006). Is oestrogen receptor-beta a predictor of endocrine therapy responsiveness in human breast cancer?&quot;,
  187. (1997). Kerato-epithelin mutations in four 5q31-linked corneal dystrophies&quot;,
  188. (2006). Keratoepithelin suppresses the progression of experimental human neuroblastomas&quot;,
  189. (2002). Lack of functional pRb results in attenuated recovery of mRNA synthesis and increased apoptosis following UV radiation in human breast cancer cells&quot;,
  190. (2000). Lack of RB protein correlates with increased sensitivity to UV-radiation-induced apoptosis in human breast cancer cells&quot;,
  191. (1996). Laser capture microdissection&quot;,
  192. (2009). Leucine-rich repeat kinase 2 phosphorylates brain tubulin-beta isoforms and modulates microtubule stability--a point of convergence in parkinsonian neurodegeneration?&quot;,
  193. (2009). Lifestyle changes and breast cancer prognosis: a review&quot;, Breast cancer research and treatment,
  194. (1990). Linkage of early-onset familial breast cancer to chromosome 17q21&quot;, Science
  195. (1994). Localization of a breast cancer susceptibility gene, BRCA2, to chromosome 13q12-13&quot;, Science
  196. (1978). Long-term human breast carcinoma cell lines of metastatic origin: preliminary characterization&quot;,
  197. (2004). Loss of antigenicity in stored sections of breast cancer tissue microarrays&quot;, Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology,
  198. (1989). Loss of antigens from immunoblotting membranes&quot;,
  199. (2006). Loss of Betaig-h3 protein is frequent in primary lung carcinoma and related to tumorigenic phenotype in lung cancer cells&quot;, Molecular carcinogenesis,
  200. (2006). MCM proteins and DNA replication&quot;, Current opinion in cell biology,
  201. (2009). MCM2 and MCM5 as prognostic markers in colon cancer: a worthwhile approach&quot;, Digestive diseases and sciences,
  202. (2005). Mechanisms of estrogen receptor signaling: convergence of genomic and nongenomic actions on target genes&quot;,
  203. (1998). Mechanisms of inactivation of E-cadherin in breast cancer cell lines&quot;,
  204. (1997). Mechanisms restricting DNA replication to once per cell cycle: the role of Cdc6p and ORC&quot;, Trends in cell biology,
  205. (2005). Minichromosome maintenance proteins 2 Koukourakis,
  206. (2005). Mitogenic effects of the upregulation of minichromosome maintenance proteins in anaplastic thyroid carcinoma&quot;, The Journal of clinical endocrinology and metabolism,
  207. (2009). Moderate alcohol intake and cancer incidence in women&quot;,
  208. (2006). Molecular architecture and assembly of the DDB1-CUL4A ubiquitin ligase machinery&quot;,
  209. (2005). Molecular evolution of breast cancer&quot;,
  210. (2005). Molecular pathology of ataxia telangiectasia&quot;,
  211. (2000). Molecular portraits of human breast tumours&quot;,
  212. (1989). Mutations in the p53 gene occur in diverse human tumour types&quot;,
  213. (1988). Neu-protein overexpression in breast cancer. Association with comedo-type ductal carcinoma in situ and limited prognostic value in stage II breast cancer&quot;, The New England journal of medicine,
  214. (2005). Night work and breast cancer risk: a systematic review and meta-analysis&quot;, European journal of cancer
  215. (2007). Non-operative breast pathology: lobular neoplasia&quot;,
  216. (2001). Nottingham Breast Team
  217. (2009). Novel multicellular organotypic models of normal and malignant breast: tools for dissecting the role of the microenvironment in breast cancer progression&quot;,
  218. (2009). Oestrogen-receptor-positive breast cancer: towards bridging histopathological and molecular classifications&quot;,
  219. (1992). Oncogenic forms of p53 inhibit p53-regulated gene expression&quot;,
  220. (2004). Osborne Kent C
  221. (2008). Overview of breast cancer staging and surgical treatment options&quot;,
  222. (2007). p53 gain-of-function cancer mutants induce genetic instability by inactivating ATM&quot;,
  223. (2009). P53 Polymorphisms: Cancer Implications&quot;,
  224. (1991). Pathological prognostic factors in breast cancer. I. The value of histological grade in breast cancer: experience from a large study with long-term follow-up&quot;,
  225. (1992). Pathological prognostic factors in breast cancer. II. Histological type. Relationship with survival in a large study with long-term follow-up&quot;,
  226. (1994). Pathological prognostic factors in breast cancer. III. Vascular invasion: relationship with recurrence and survival in a large study with long-term follow-up&quot;,
  227. (1994). PDGF- and insulin-dependent pp70S6k activation mediated by phosphatidylinositol-3-OH kinase&quot;,
  228. (2009). Physical activity and breast cancer risk among pre- and postmenopausal women in the U.S. Radiologic Technologists cohort&quot;,
  229. (2007). Physical activity and breast cancer: a systematic review&quot;, Epidemiology
  230. (2006). Polymorphisms in DNA damage binding protein 2 (DDB2) and susceptibility of primary lung cancer in the Chinese: a case-control study&quot;,
  231. (2000). Pooled analysis of prospective cohort studies on height, weight, and breast cancer risk&quot;,
  232. (2007). Poor prognosis in carcinoma is associated with a gene expression signature of aberrant PTEN tumor suppressor pathway activity&quot;,
  233. (2000). Primer3 on the WWW for general users and for biologist programmers&quot;,
  234. (2004). Prognostic relevance of histological grade and its components in node-negative breast cancer patients&quot;, Modern pathology : an official journal of the United States and Canadian Academy of Pathology,
  235. (1993). Prognostic significance of benign proliferative breast disease&quot;,
  236. (2000). Prognostic significance of young age in breast cancer&quot;,
  237. (2000). Prognostic value of histologic grade and proliferative activity in axillary node-positive breast cancer: results from the Eastern Cooperative Oncology Group Companion Study, EST 4189&quot;,
  238. (2009). Prohibitin physically interacts with MCM proteins and inhibits mammalian DNA replication&quot;,
  239. (2003). Proteomic analysis of post-translational modifications&quot;,
  240. (2007). PTEN enters the nuclear age&quot;,
  241. (2006). Quantification of immunohistochemistry--issues concerning methods, utility and semiquantitative assessment I&quot;,
  242. (2002). Quantification of mRNA using real-time reverse transcription PCR (RTPCR): trends and problems&quot;,
  243. (2005). Quantitation of CDC6 and MCM5 mRNA in cervical intraepithelial neoplasia and invasive squamous cell carcinoma of the cervix&quot;, Modern pathology : an official journal of the United States and Canadian Academy of Pathology,
  244. (2003). Rating the risk factors for breast cancer&quot;,
  245. (1996). Recommendations for the reporting of breast carcinoma. Human Pathol
  246. (2008). Recurrent gross mutations of the PTEN tumor suppressor gene in breast cancers with deficient DSB repair&quot;,
  247. (2000). Relationship between c-erbB-2 and other tumor characteristics in breast cancer prognosis&quot;,
  248. (1994). Relationship of transforming growth factor beta 1 to extracellular matrix and stromal infiltrates in invasive breast carcinoma&quot;,
  249. (2004). Relevance of breast cancer cell lines as models for breast tumours: an update&quot;, Breast cancer research and treatment,
  250. (2005). Reliable gene expression measurements from degraded RNA by quantitative real-time PCR depend on short amplicons and a proper normalization&quot;, Laboratory investigation; a journal of technical methods and pathology,
  251. (2003). Repeated observation of breast tumor subtypes in independent gene expression data sets&quot;,
  252. (1993). Reproductive factors and breast cancer&quot;,
  253. (2010). Reproductive factors, exogenous female hormone use and breast cancer risk in Japanese: the Miyagi Cohort Study&quot;,
  254. (1999). Requirement of ATM-dependent phosphorylation of brca1 in the DNA damage response to double-strand breaks&quot;,
  255. (1995). Resistance to transforming growth factor beta and activin due to reduced receptor expression in human breast tumor cell lines&quot;,
  256. (2001). Responsiveness to transforming growth factor-beta (TGF-beta)-mediated growth inhibition is a function of membrane-bound TGF-beta type II receptor in human breast cancer cells&quot;,
  257. (2002). Revision of the American Joint Committee on Cancer staging system for breast cancer&quot;,
  258. (1999). RGD peptides induce apoptosis by direct caspase-3 activation&quot;,
  259. (2004). Risk of cancer from diagnostic X-rays: estimates for the UK and 14 other countries&quot;,
  260. (2000). Role of HER2 gene overexpression in breast carcinoma&quot;,
  261. (2004). Role of transforming growth factor beta in breast carcinogenesis&quot;,
  262. (2003). Roles of BRCA1 in DNA damage repair: a link between development and cancer&quot;, Human molecular genetics,
  263. (1988). Second-strand cDNA synthesis with E. coli DNA polymerase I and RNase H: the fate of information at the mRNA 5' terminus and the effect of E. coli DNA ligase&quot;,
  264. (2001). Secreted and cell surface genes expressed in benign and malignant colorectal tumors&quot;,
  265. (1998). Selection of potentially metastatic subpopulations expressing c-erbB-2 from breast cancer tissue by use of an extravasation model&quot;, The American journal of pathology,
  266. (2002). Sequential binding of UV DNA damage binding factor and degradation of the p48 subunit as early events after UV irradiation&quot;,
  267. (1999). Significance of axillary lymph node metastasis in primary breast cancer&quot;,
  268. (1974). Size and location of the transforming region in human adenovirus type 5 DNA&quot;,
  269. (2008). Sleep duration and the risk of breast cancer: the Ohsaki Cohort Study&quot;,
  270. (2005). Solving the dilemma of the immunohistochemical and other methods used for scoring estrogen receptor and progesterone receptor in patients with invasive breast carcinoma&quot;,
  271. (2005). Sporadic breast cancer in young women a microarray investigation,
  272. (2002). Sporadic breast cancer in young women: prevalence of loss of heterozygosity at p53, BRCA1 and BRCA2&quot;,
  273. (2002). Staurosporine-induced G(1) arrest in cancer cells depends on an intact pRB but is independent of p16 status&quot;,
  274. (2001). Steering Committee on Clinical Practice Guidelines for the Care and Treatment of Breast Cancer
  275. (2007). Structural changes in Mcm5 protein bypass Cdc7-Dbf4 function and reduce replication origin efficiency in Saccharomyces cerevisiae&quot;, Molecular and cellular biology,
  276. (2000). Studies of the murine DDB1 and DDB2 genes&quot;,
  277. (2003). Study Collaborators
  278. (2002). Studying actin-dependent processes in tissue culture&quot;,
  279. (1995). Substitution of chloroform by bromo-chloropropane in the single-step method of RNA isolation&quot;,
  280. (2004). Survival after surgical treatment of breast cancer&quot;,
  281. (1990). Target amplification for DNA analysis by the polymerase chain reaction&quot;,
  282. (2001). TGF-beta signaling in cancer--a double-edged sword&quot;, Trends in cell biology,
  283. (2001). TGF-beta signaling in tumor suppression and cancer progression&quot;,
  284. (2008). TGFbeta-induced protein mediates lymphatic endothelial cell adhesion to the extracellular matrix under low oxygen conditions&quot;, Cellular and molecular life sciences : CMLS,
  285. (2009). TGFBI deficiency predisposes mice to spontaneous tumor development&quot;,
  286. (2006). TGFBI gene mutations in corneal dystrophies&quot;,
  287. (2007). TGFBIp/betaig-h3 protein: a versatile matrix molecule induced by TGF-beta&quot;,
  288. (2008). The analysis of novel gene targets in breast cancer in women <35 years,
  289. (2006). The ATM missense mutation p.Ser49Cys (c.146C>G) and the risk of breast cancer&quot;,
  290. (1998). The BRC repeats in BRCA2 are critical for RAD51 binding and resistance to methyl methanesulfonate treatment&quot;,
  291. (2010). The contribution of gene expression profiling to breast cancer classification, prognostication and prediction: a retrospective of the last decade&quot;,
  292. (2003). The diagnosis and management of pre-invasive breast disease: genetic alterations in pre-invasive lesions&quot;,
  293. (2003). The diagnosis and management of pre-invasive breast disease: pathology of atypical lobular hyperplasia and lobular carcinoma in situ&quot;,
  294. (1989). The epidemiology of serum sex hormones in postmenopausal women&quot;,
  295. (2010). The Expression Patterns
  296. (1986). The gene for human p53 cellular tumor antigen is located on chromosome 17 short arm (17p13)&quot;,
  297. (1998). The HER-2/neu oncogene in breast cancer: prognostic factor, predictive factor, and target for therapy&quot;, Stem cells
  298. (1984). The impact of pathology on the biologic, diagnostic, prognostic, and therapeutic considerations in breast cancer&quot;,
  299. (2010). The influence of common polymorphisms on breast cancer&quot;,
  300. (1994). The inherited component of cancer&quot;,
  301. (1974). The interaction of phalloidin. Some of its derivatives, and of other cyclic peptides with muscle actin as studied by viscosimetry&quot;,
  302. (1977). The measurement of observer agreement for categorical data&quot;,
  303. (2005). The molecular genetics of breast cancer: the contribution of comparative genomic hybridization&quot;, Pathology, research and practice,
  304. (2006). The molecular portraits of breast tumors are conserved across microarray platforms&quot;,
  305. (1998). The National Cancer Data Base 10-year survey of breast carcinoma treatment at hospitals in the United States&quot;,
  306. (1992). The Nottingham Prognostic Index in primary breast cancer&quot;, Breast cancer research and treatment,
  307. (2001). The p48 subunit of the damaged-DNA binding protein DDB associates with the CBP/p300 family of histone acetyltransferase&quot;,
  308. (2005). The pathology of breast cancer and the role of the histopathology laboratory&quot;,
  309. (1975). The pathology of invasive breast cancer. A syllabus derived
  310. (2005). The power of real-time PCR&quot;,
  311. (1986). The relation between survival and age at diagnosis in breast cancer&quot;, The New England journal of medicine,
  312. (2008). The role of the pathologist in assessing prognostic factors for breast cancer. Prognostic and predictive factors
  313. (2001). The surgical management of early breast cancer&quot;,
  314. (2008). The TGF-beta-induced gene product, betaig-h3: its biological implications in peritoneal dialysis&quot;, Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association -
  315. (2002). The transforming growth factor-beta-inducible matrix protein (beta)ig-h3 interacts with fibronectin&quot;,
  316. (2003). The ubiquitin ligase activity in the DDB2 and CSA complexes is differentially regulated by the COP9 signalosome in response to DNA damage&quot;,
  317. (1994). Three autosomal dominant corneal dystrophies map to chromosome 5q&quot;,
  318. (2009). Tiling path genomic profiling of grade 3 invasive ductal breast cancers&quot;, Clinical cancer research : an official journal of the American Association for Cancer Research,
  319. (1998). Tissue architecture: the ultimate regulator of epithelial function?&quot;,
  320. (1995). Transforming growth factor beta and cell cycle regulation&quot;,
  321. (2000). Transforming growth factor-beta and breast cancer: Transforming growth factor-beta/SMAD signaling defects and cancer&quot;,
  322. (2005). Treatment results and prognostic factors of early breast cancer treated with a breast conserving operation and radiotherapy&quot;, Japanese journal of clinical oncology,
  323. (2005). Tumor-prone phenotype of the DDB2-deficient mice&quot;,
  324. (2009). Tumour-associated tenascin-C isoforms promote breast cancer cell invasion and growth by matrix metalloproteinase-dependent and independent mechanisms&quot;,
  325. (2008). Two novel VHL targets, TGFBI (BIGH3) and its transactivator KLF10, are upregulated in renal clear cell carcinoma and other tumors&quot;, Biochemical and biophysical research communications,
  326. (2001). UCN-01 (7-hydoxystaurosporine) inhibits in vivo growth of human cancer cells through selective perturbation of G1 phase checkpoint machinery&quot;,
  327. (2009). University of Leicester, &quot; Molecular cloning and functional studies of tenascin-C isoforms containing the fibronectin-type III repeat additional domain 1 (AD1) &quot;,
  328. (2006). Up-regulated transforming growth factor beta-inducible gene h3 in rheumatoid arthritis mediates adhesion and migration of synoviocytes through alpha v beta3 integrin: Regulation by cytokines&quot;,
  329. (1988). UV mutagenic photoproducts in Escherichia coli and human cells: a molecular genetics perspective on human skin cancer&quot;, Photochemistry and photobiology,
  330. (2001). UV-damaged DNA-binding proteins are targets of CUL-4A-mediated ubiquitination and degradation&quot;,
  331. (2006). Validation and clinical utility of a 70-gene prognostic signature for women with node-negative breast cancer&quot;,
  332. (2009). Validation of 70-gene prognosis signature in node-negative breast cancer&quot;, Breast cancer research and treatment,
  333. (2002). Very young women (<35 years) with operable breast cancer: features of disease at presentation&quot;, Annals of Oncology :
  334. (2006). Vitamin D, calcium, and breast cancer risk: a review&quot;, Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology,
  335. (2004). Women's Health Initiative Steering Committee
  336. (2005). Xeroderma pigmentosum complementation group E protein (XPE/DDB2): purification of various complexes of XPE and analyses of their damaged DNA binding and putative DNA repair properties&quot;, Molecular and cellular biology,
  337. (2008). Young age at diagnosis correlates with worse prognosis and defines a subset of breast cancers with shared patterns of gene expression&quot;,
  338. (1996). Younger women with breast carcinoma have a poorer prognosis than older women&quot;,

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