Kalra , R.S. and Bapat , S.A. (2013) Enhanced levels of double-strand DNA break repair proteins protect ovarian cancer cells against genotoxic stress-induced apoptosis. Journal of Ovarian Cancer , 6 (66). pp. 1-12.

Text 20. Dr. Bapat S. (Jr. of Ova. Can.) Open Access-c@author.pdf - Published Version Restricted to Registered users only Download (517Kb) | Request a copy

Abstract

Background: Earlier, proteomic profiling of a Serous Ovarian Carcinoma (SeOvCa) progression model in our lab had identified significantly enriched expression of three double-strand break (DSB) -repair proteins viz. RAD50, NPM1, and XRCC5 in transformed cells over pre-transformed, non-tumorigenic cells. Analysis of the functional relevance of enhanced levels of these proteins was explored in transformed ovarian cancer cells. Methods: Expression profiling, validation and quantitation of the DSB-repair proteins at the transcriptional and protein levels were carried out. Further analyses included identification of their localization, distribution and modulation on exposure to Estradiol (E2) and cisplatin. Effects on silencing of each of these under conditions of genomic-stress were studied with respect to apoptosis, alterations in nuclear morphology and DNA fragmentation; besides profiling known mitotic and spindle check-point markers in DSB-repair. Results: We identified that levels of these DSB-repair proteins were elevated not only in our model, but generally in cancer and are specifically triggered in response to genotoxic stress. Silencing of their expression led to aberrant DSB repair and consequently, p53/p21 mediated apoptosis. Further compromised functionality generated genomic instability. Conclusions: Present study elucidates a functional relevance of NPM1, RAD50 and XRCC5 DSB-repair proteins towards ensuring survival and evasion of apoptosis during ovarian transformation, emphasizing their contribution and association with disease progression in high-grade SeOvCa. Keywords: SeOvCa progression model, DSB-repair, HR and NHEJ pathways, Aneuploidy

Item Type:	Article
Additional Information:	This is Open Access Journal (fro full text click above Web link)
Subjects:	Cancer Biology
Depositing User:	Mr. Rameshwar Nema
Date Deposited:	22 Apr 2015 09:53
Last Modified:	30 Jun 2015 11:24
URI:	http://nccs.sciencecentral.in/id/eprint/100

Actions (login required)

View Item