beta-catenin gene mutation in invasive ductal breast cancer

Purpose: Aberrant accumulation of beta-catenin plays an important role in a variety of human neoplasms. In this study we analyzed the somatic mutations of the beta-catenin gene and the immunohistochemical localization of beta-catenin and cyclin D1 in invasive ductal breast cancer

Vitamin D receptor gene polymorphisms and male breast cancer risk in Turkish population

Purpose: Male breast cancer (MBC) is a rare disease. However; as global populace ages, there is a trend for MBC increase. Although its etiology is still unclear, constitutional, environmental, hormonal (abnormalities in estrogen/androgen balance) and genetic (positive family history, Klinefelter syndrome, mutations in BRCA1 and BRCA2) risk factors are already known. One potential target is the vitamin D receptor (VDR). We have investigated whether polymorphisms in the VDR gene are associated with altered MBC risk in a Turkish population

Microsatellite instability is not a common feature in medullary breast cancer

Microsatellite instability (MSI) is a form of genomic instability associated with defective DNA mismatch repair in tumors. MSI is found in 85-90% of hereditary nonpolyposis colorectal cancer cases; however, its occurrence in breast carcinogenesis still remains to be clarified. In addition, data are limited on the incidence of MSI in the medullary subtype. The purpose of this study was to investigate the occurrence of MSI in medullary breast cancer (MBC). The study included a total of 16 patients with MBC, nine with typical and seven with atypical histology. The incidence of MSI in five microsatellite loci (D2S123, D3S1611, D17S807, D17S796 and Xq11-12) was determined by comparing paired normal and tumor tissue DNA after PCR amplification from paraffin-embedded tissues. All 16 tumors showed stability at five loci. Although the number of microsatellite markers and DNA samples may limit the value of our results, we conclude that the MSI phenotype is uncommon in human MBC. (C) 2002 Elsevier Science Ltd. All rights reserved

Full-length cDNA sequence and genomic organization of human NKX3A - alternative forms and regulation by both androgens and estrogens

NKX3A (NKX3.1) is a recently identified androgen-regulated gene that is largely specific to prostate for expression and likely to code for a homeobox protein. Here we report the full-length mRNA and genomic organization of human NKX3.1. There are at least five different splice variants of NKX3.1 mRNA that result in different open reading frames (ORFs). There is extensive similarity between the human and the mouse NKX3.1 cDNA sequences outside of the ORFs (greater than 60% overall identity), which may be involved in modulating NKX3.1 expression. In addition to its androgen regulation in the prostate cancer cell line LNCaP, we show that NKX3.1 expression is androgen-dependent in the CWR22 prostate cancer xenograft model. Interestingly, NKX3.1 is highly expressed in the androgen-independent derivative CWR22R in the absence of androgens, indicating that it may be deregulated in advanced prostate cancer. Using a Green Flourescent Protein fusion construct, we show that NKX3.1 is a nuclear protein consistent with its proposed function as a homeobox transcription factor. Furthermore, in addition to androgens, NKX3.1 expression is up-regulated by 17 beta -estradiol, but not by progesterone, dexamethasone, or 3,5,3'-triiodothyronine in LNCaP cells. Regulation of NKX3.1 by androgens and 17 beta -estradiol in prostate cancer cells and its deregulation in androgen-independent prostate cancer suggest that it may have important regulatory roles during prostate cancer progression. (C) 2000 Elsevier Science B.V. All rights reserved

Consistent loss of heterozygosity at 14q32 in lymphoid blast crisis of chronic myeloid leukemia

Little is understood about the basic biological mechanisms that underlie the reasons for acute transformation in chronic myeloid leukemia (CML). Progression of disease may include inactivation of one or more tumor suppressor genes (TSGs). A widely used methodology for indirectly detecting somatic inactivation of TSGs is searching loss of heterozygosity (LOH) for polymorphic loci located in or near the gene(s) of interest. We aimed to analyze DNA of chronic phase and blastic phase archive material of 15 CML patients for LOH using D1S-430, D2S123, D3S1611, D11S29, D14S65, D17S520, BAT 40 markers, the dinucleotide repeat located in the ABL gene and the trinucleotide repeat located in the BCR gene (amplification of the trinucleotide in the BCR gene could not be succeeded). LOH was identified by a %50 lost of one of the alleles intensity. LOH was detected with the ABL dinucletide repeat and D2S123 marker in two patients and with the D14S65 marker in three patients. The three patients exhibiting LOH at the D14S65 locus, all proceeded through lymphoid blast crisis. The D14S65 marker is located at the 14q32 locus which contains the immunglobulin heavy chain gene and the TCL1 oncogene. 14q32 abnormalities at the molecular level, may be predictive for lymphoid blast crisis, whether or not they are detectable cytogenetically

Microsatellite instability in early-onset breast cancer

Breast cancer in a young person is considered a rare and very aggressive disease. The theories addressing the underlying genetic mechanisms of this disease are controversial. Therefore, additional genetic concepts playing a possible role in its pathogenesis and prognosis must be investigated. Microsatellite instability (MSI) characterized by a mutational process of insertions or deletions in microsatellite repeats might constitute a sensitive indicator for genomic instability in cancer. MSI has been described in a wide variety of tumors, particularly in hereditary non-polyposis colorectal cancer. The reports regarding its occurrence and prognostic significance in breast cancer are in conflict with each other. The purpose of this study was to investigate MSI in early-onset breast cancer and to correlate its occurrence with clinicopatbological prognisticators. In this study, 16 female patients with primary breast cancer under 35 years of age (range 29-34) were investigated for the incidence of MSI in five microsatellite loci (D2S123, D3S1611, D17S807, D17S796 and Xq11-12) by comparing paired normal and tumor tissue DNA after PCR amplification from paraffin-embedded tissues. No instability was found in any of these five microsatellite loci. Although care must be taken not to overstate the importance of this result due to the inadequate number of microsatellite markers and DNA samples studied, this preliminary report indicates that MSI phenotype is uncommon in human early-onset breast cancer. Therefore, it does not appear to be related to the prognosis of disease

Role of transforming growth factor-beta 1 gene polymorphisms in childhood idiopathic thrombocytopenic purpura

Purpose: To investigate whether transforming growth factor-PI (TGF-beta1) gene polymorphisms have a role in the development, clinical progress, and treatment response in children with idiopathic thrombocytopenic purpura (ITP)

NOVEL ANGIOGENESIS INHIBITOR BEVACIZUMAB INDUCES APOPTOSIS IN THE RAT ENDOMETRIOSIS MODEL

Our aim was to investigate the effects of anti-vascular endothelial growth factor (anti-VEGF) antibody Bevacizumab on endometrial explants and on apoptotic gene expression levels in the rat endometriosis model. Endometriotic implants were surgically formed, and rats treated with (i) 1 mg/kg single subcutaneous injection of depot leuprolide acetate; (ii) 2.5 mg/kg of single intaperitoneal injection of bevacizumab; (iii) intraperitoneal injection of saline. Histopathologic scores and adhesion scores of endometriotic foci and levels of Bcl-2-associated X protein (Bax), Cytochrome c (Cyt-c), B-cell lymphoma/leukemia 2 (Bcl-2) and B-cell lymphoma-extra large (Bcl-xl) mRNA gene expressions of endometriotic foci. Bevacizumab treatment decreased the endometriotic explant size compared with control. Bevacizumab-treated rats had lower total adhesion scores when compared with the control group. Semi-quantitative evaluation of the persistence of endometrial epithelial cells in the explants showed a lower score in gonadotropin-releasing hormone (GnRH) agonist-treated rats compared with control rats. In Bevacizumab increased expression of Bax 3.1-fold, Cyt-c 1.3-fold and decreased expression of Bcl-2 0.4-fold, Bcl-xl 0.8-fold compared with the control group. The GnRH agonist increased expression of Bax 3.0 fold, Cyt-c 1.3 fold and decreased expression of Bcl-2 0.4-fold, Bcl-xl 0.8-fold, compared with the control group. This study suggests that a novel angiogenesis inhibitor, anti-VEGF antibody bevacizumab is as effective as GnRH agonist in the regression of the endometriotic lesions in rat endometriosis model. One possible mechanism of this effect is the induction of apoptosis