کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8259038 | 1534630 | 2016 | 13 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Frequent inactivation of MCC/CTNNBIP1 and overexpression of phospho-beta-cateninY654 are associated with breast carcinoma: Clinical and prognostic significance
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کلمات کلیدی
MsrATNBCUICC5-Aza-dCHER2TNMHRPNuclear β-cateninqRT-PCR5-Aza-2′-deoxycytidine - 5-Aza-2'-deoxycytidineInternational Union Against Cancer - اتحادیه بین المللی سرطانBreast cancer subtypes - زیر گونه سرطان پستانTriple negative breast cancer - سرطان سینه سه گانه منفیBreast cancer - سرطان پستانbreast carcinoma - کارسینوم سینه، کارسینوم پستانEstrogen receptor - گیرنده استروژنHuman epidermal growth factor receptor 2 - گیرنده عامل فاکتور رشد اپیدرمی انسان 2Progesterone receptor - گیرنده پروژسترون
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
سالمندی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Transcriptional activation of β-catenin is a hallmark of Wnt/β-catenin pathway activation. The MCC (Mutated in colorectal cancers) and CTNNBIP1 (catenin, beta interacting protein 1) are two candidate genes which inhibit the transcriptional activity of nuclear β-catenin. The importance of MCC and CTNNBIP1 in breast cancer (BC) development has not yet been studied in detail. For this reason, in present study, the alterations (deletion/methylation/mutation/expression) of MCC and CTNNBIP1 were analyzed in BC of Indian patients (N = 120) followed by expression/mutation analysis of β-catenin. Then transcriptional activity of β-catenin was checked by expression analysis of its target genes (EGFR, C-MYC and CCND1) in the same set of samples. Frequent methylation (44-45%) than deletion (20-32%) with overall alterations of 52-55% was observed in MCC/CTNNBIP1 in the BC samples. The alterations of MCC/CTNNBIP1 showed significant correlation with increased nuclear β-catenin/p-β-cateninY654 expression. Also, a significant correlation was seen between nuclear β-catenin expression and overexpression of its target genes like EGFR, MYC and CCND1 in the BC samples (P < 0.0001). An upregulation of MCC and CTNNBIP1 expression by 5-Aza-2â²-deoxycytidine treatment of MCF7 and MDA-MB-231 cell lines lead to downregulation of β-catenin and its target genes. The expression of nuclear p-β-cateninY654, EGFR, MYC and CCND1 were significantly high in TNBC (Triple negative BC) and Her2 + compared to Luminal A/B + subtypes. The TNBC patients in stage III/IV having reduced expression of MCC in the tumors showed poor prognosis. Thus, our data suggests that inactivation of MCC/CTNNBIP1 could be an important event in activation of β-catenin mediated transcription of target genes in BC.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease - Volume 1862, Issue 9, September 2016, Pages 1472-1484
Journal: Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease - Volume 1862, Issue 9, September 2016, Pages 1472-1484
نویسندگان
Nupur Mukherjee, Hemantika Dasgupta, Rittwika Bhattacharya, Debolina Pal, Rituparna Roy, Saimul Islam, Neyaz Alam, Jaydip Biswas, Anup Roy, Susanta Roychoudhury, Chinmay Kumar Panda,