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Cell Polarity, Epithelial-Mesenchymal Transition, and Cell-Fate Decision Gene Expression in Ductal Carcinoma In Situ

By Danila Coradini, Patrizia Boracchi, Federico Ambrogi, Elia Biganzoli and Saro Oriana

Abstract

Loss of epithelial cell identity and acquisition of mesenchymal features are early events in the neoplastic transformation of mammary cells. We investigated the pattern of expression of a selected panel of genes associated with cell polarity and apical junction complex or involved in TGF-β-mediated epithelial-mesenchymal transition and cell-fate decision in a series of DCIS and corresponding patient-matched normal tissue. Additionally, we compared DCIS gene profile with that of atypical ductal hyperplasia (ADH) from the same patient. Statistical analysis identified a “core” of genes differentially expressed in both precursors with respect to the corresponding normal tissue mainly associated with a terminally differentiated luminal estrogen-dependent phenotype, in agreement with the model according to which ER-positive invasive breast cancer derives from ER-positive progenitor cells, and with an autocrine production of estrogens through androgens conversion. Although preliminary, present findings provide transcriptomic confirmation that, at least for the panel of genes considered in present study, ADH and DCIS are part of a tumorigenic multistep process and strongly arise the necessity for the regulation, maybe using aromatase inhibitors, of the intratumoral and/or circulating concentration of biologically active androgens in DCIS patients to timely hamper abnormal estrogens production and block estrogen-induced cell proliferation

Topics: Research Article
Publisher: Hindawi Publishing Corporation
OAI identifier: oai:pubmedcentral.nih.gov:3335180
Provided by: PubMed Central
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    1. (2004). A b dE l - R e h i m ,S .E .P i n d e r ,C .E .P a i s he ta l .
    2. A practical and powerful approach to multiple testing,” JournalofRoyalStatisticalSocietyB,vol.57,pp.284–300,1995.
    3. (2007). Abrogated response to cellular stress identifies DCIS associated with subsequent tumor events and defines basal-like breast tumors,”
    4. (2008). Activation of Wnt signalling in acute myeloid leukemia by induction of
    5. (1992). Applied Multivariate Data Analysis. Volume 2. Categorical and Multivariate Methods,
    6. (2004). Breast cancer, stem/progenitor cells and the estrogen receptor,”
    7. (2011). C.Casarsa,N.Bassani,F.Ambrogietal.,“Epithelial-to-mesenchymal transition, cell polarity and stemness-associated features in malignant pleural mesothelioma,”
    8. (2009). Cancer stem cells in breast cancer and metastasis,”
    9. (2005). CD24 staining of mouse mammary gland cells defines luminal epithelial, myoepithelial/basal and nonepithelial cells,”
    10. (2007). Cell polarity in development and cancer,”
    11. (2011). Comparison of increased aromatase versus ERα in the generation of mammary hyperplasia and cancer,”
    12. (2007). Coppe et al., “Novel definition files for human GeneChips based on
    13. (2011). Crosstalk of TGF-β and estrogen receptor signaling in breast cancer,”
    14. (2008). Ductal carcinoma in situ and the emergence of diversity during breast cancer evolution,”
    15. (2010). Ductal carcinoma in Situ of the breast: a systematic review of incidence, treatment, and outcomes,”
    16. (2009). Ductal carcinoma in situ: state of the science and roadmap to advance the field,”
    17. (2009). Early dysregulation of cell adhesion and extracellular matrix pathways in breast cancer progression,”
    18. (2007). EGFR associated expression profiles vary with breast tumor subtype,”
    19. (2009). Epithelial to mesenchymal transition and breast cancer,”
    20. (2009). Epithelial-mesenchymal transition in development and cancer,”
    21. (2010). Epithelialmesenchymal transition (EMT) in tumor-initiating cells and its clinical implications in breast cancer,”
    22. (2008). Evidence that molecular changes in cells occur before morphological alterationsduringtheprogressionofbreastductalcarcinoma,”
    23. (2010). F.Husson,S.Lˆ e,andJ.Pag` es,ExploratoryMultivariateAnalysis by Example Using R, Computer Science and Data Analysis Series,
    24. (2011). From milk to malignancy: the role of mammary stem cells in development, pregnancy and breast cancer,”
    25. (2007). Gata3 is an essential regulator of mammary-gland morphogenesis and luminal-cell differentiation,”
    26. (2008). Generation of breast cancer stem cells through epithelial-mesenchymal transition,”
    27. (2006). Genome-wide mapping of polycomb target genes unravels their roles
    28. (2008). H.Kouros-Mehr,J.W.Kim,S.K.Bechis,andZ.Werb,“GATA3 and the regulation of the mammary luminal cell fate,”
    29. (2009). HER2/neu expression correlates with vascular endothelial growth factorC and lymphangiogenesis in lymph node-positive breast cancer,”
    30. (2004). Hormonal regulation of metastasis-associated protein 3 transcription in breast cancer cells,”
    31. (2008). Integrated genomic and transcriptomic analysis of ductal carcinoma in situ of the breast,”
    32. (2008). Intratumoral concentration of sex steroids and expression of sex steroidproducing enzymes in ductal carcinoma in situ of human breast,”
    33. (2008). Intratumoral estrogen production in breast carcinoma: significance of aromatase,”
    34. (2005). Isolation and in vitro propagation of tumorigenic breast cancer cells with stem/ progenitor cell properties,”
    35. (2005). Kemming et al., “Upregualtion of gene expression by hypoxia is mediated predominantly by hypoxia-inducible factor
    36. (2000). M¨ uller, “Genetic control of epithelial cell polarity: lessons from
    37. (2010). Malignant precursor cells pre-exist in human breast DCIS and require autophagy for survival,” PLoS One,v o l .5 ,n o .4 ,A r t i c l eI D e10240,
    38. (2009). Mechanism of TGF-β signaling to growth arrest, apoptosis, and epithelialmesenchymal transition,”
    39. (2005). Molecular evolution of breat cancer,”
    40. (2007). MTA family of coregulators in nuclear receptor biology and pathology,”
    41. (2009). NIH state-ofthe-science conference statement: diagnosis and management ofductalcarcinomainsitu(DCIS),”NIHConsensusandStateof-the-Science Statements,
    42. (2009). Normal and cancerrelated functions of the p160 steroid receptor co-activator (SRC) family,”
    43. (2005). Outcome of patients with ductal carcinoma in situ untreated after diagnostic biopsy: results from the nurses’ health study,”
    44. (2009). p21CIP1 attenuates Ras- and c-Myc-dependent breast tumor epithelial mesenchymal transition and cancer stem cell-like gene expression in vivo,”
    45. (2010). Preinvasive breast cancer,”
    46. (2010). Prognostic impact of the expression of putative cancer stem cell markers CD133, CD166, CD44s, EpCAM, and ALDH1 in colorectal cancer,”
    47. (2008). Regulation of cell polarity during epithelial morphogenesis,”
    48. Role of Notch signaling in cell-fate determination of human mammary stem/progenitor cells,”BreastCancerResearch,vol.6,no.6,pp.R605–615,2004.
    49. (2010). Spring Harbor perspectives in biology,
    50. (2001). TGF-β signaling in tumor suppression and cancer progression,”
    51. (2009). TGF-β-induced epithelial to mesenchymal transition,”
    52. (2011). The potency and clinical efficacy of aromatase inhibitors across the breast cancer continuum,”
    53. (2008). Transcriptional regulation of cell polarity
    54. (2008). u d e l i s t ,P .W ¨ ulfing, C. Kersting et al., “Expression of aromatase and estrogen sulfotransferase in preinvasive and invasive breast cancer,”

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