Bcl-2/adenovirus E1B 19 kDa-interacting protein 3 (BNIP3) expression is epigenetically regulated by one-carbon metabolism in invasive duct cell carcinoma of breast

作     者：Naushad, Shaik Mohammad Prayaga, Aruna Digumarti, Raghunadha Rao Gottumukkala, Suryanarayana Raju Kutala, Vijay Kumar 

作者机构：Nizams Inst Med Sci Dept Clin Pharmacol & Therapeut Hyderabad 500082 Andhra Pradesh India Nizams Inst Med Sci Dept Pathol Hyderabad 500082 Andhra Pradesh India Nizams Inst Med Sci Dept Med Oncol Hyderabad 500082 Andhra Pradesh India Nizams Inst Med Sci Dept Surg Oncol Hyderabad 500082 Andhra Pradesh India 

出 版 物：《MOLECULAR AND CELLULAR BIOCHEMISTRY》 (分子与细胞生物化学)

年 卷 期：2012年第361卷第1-2期

页      面：189-195页

核心收录：

学科分类：0710[理学-生物学] 071010[理学-生物化学与分子生物学] 07[理学] 

基　　金：Indian Council of Medical Research (ICMR), New Delhi [5/13/32/2007] Department of Science and Technology, Government of India 

主　　题：BNIP3 One-carbon metabolism CpG island methylator phenotype 8-Oxo-2 '-deoxyguanosine 

摘      要：In view of recent studies highlighting the prognostic relevance of expression and CpG island methylator phenotype (CIMP) of Bcl-2/adenovirus E1B 19 kDa-interacting protein 3 (BNIP3) in invasive duct cell carcinoma (IDC), we hypothesized in this article that impaired one-carbon metabolism might influence CIMP phenotype of BNIP3. In order to substantiate the prognostic relevance of BNIP3, we explored its association with 8-oxo-2 deoxyguanosine (8-oxodG), a marker of oxidative stress with prognostic relevance. BNIP3 expression and CIMP phenotype were studied using semi-quantitative RT-PCR and combined bisulfite restriction analysis (COBRA), respectively, in 56 IDC tumors. Eight polymorphisms in one-carbon metabolism were studied using PCR-RFLP and PCR-AFLP approaches. 8-oxodG was measured using competitive ELISA kit. BNIP3 was found to be upregulated in IDC (cases vs. controls: 0.94 +/- A 0.05 vs. 0.18 +/- A 0.08, P 10% methylation: 7.24 +/- A 2.77 ng/ml vs. 4.42 +/- A 2.93 ng/ml, P 0.0005);and no association with nuclear pleomorphism or mitotic index or ER, PR, and HER statuses. Synergistic effect of MTR A2756G and MTRR A66G variants on BNIP3 hypermethylator phenotype was clearly evident (P 0.0007). MTRR A66G and cSHMT C1420T polymorphisms influence CIMP phenotype of BNIP3, thus epigenetically regulating BNIP3 in breast cancer. The linear association between BNIP3 and 8-oxodG substantiates the role of BNIP3 as redox sensor as well as prognostic marker in breast cancer.