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- 题目:
- Frequent inactivation of MCC/CTNNBIP1 and overexpression of phospho-beta-catenin(Y654) are associated with breast carcinoma: Clinical and prognostic significance.
- 作者:
- Mukherjee(Nupur),Dasgupta(Hemantika),Bhattacharya(Rittwika),Pal(Debolina),Roy(Rituparna),Islam(Saimul),Alam(Neyaz),Biswas(Jaydip),Roy(Anup),Roychoudhury(Susanta),Panda(Chinmay Kumar)
- 状态:
- 发布时间2016-07-29 , 更新时间 2016-11-26
- 期刊:
- Biochim Biophys Acta
- 摘要:
- 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-catenin(Y654) 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-2'-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-catenin(Y654), 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.
- 语言:
- eng
- DOI:
- 10.1016/j.bbadis.2016.05.009
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