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

• Published in: Molecular and cellular biochemistry 2012-02, Vol.361 (1-2), p.189-195
• Main Authors: Naushad, Shaik Mohammad, Prayaga, Aruna, Digumarti, Raghunadha Rao, Gottumukkala, Suryanarayana Raju, Kutala, Vijay Kumar
• Format: Article
• Language: English
• Subjects: 5-Methyltetrahydrofolate-homocysteine S-methyltransferase; Adenovirus; Adenoviruses; Amplified Fragment Length Polymorphism Analysis; Analysis; Biochemistry; Biomedical and Life Sciences; Breast cancer; Breast Neoplasms - genetics; Breast Neoplasms - metabolism; Breast Neoplasms - pathology; Cancer; Carbon; Carcinoma; Carcinoma, Ductal, Breast - genetics; Carcinoma, Ductal, Breast - metabolism; Carcinoma, Ductal, Breast - pathology; Cardiology; Cellular biology; Deoxyguanosine - analogs & derivatives; Deoxyguanosine - metabolism; DNA Methylation; Enzyme-linked immunosorbent assay; Epigenesis, Genetic; Epigenetics; Female; Ferredoxin-NADP Reductase - genetics; Ferredoxin-NADP Reductase - metabolism; Gene Expression Regulation, Neoplastic; Genotype & phenotype; Glycine Hydroxymethyltransferase - genetics; Glycine Hydroxymethyltransferase - metabolism; Humans; Life Sciences; Medical Biochemistry; Membrane Proteins - genetics; Membrane Proteins - metabolism; Metabolism; Methylation; Oncology; Oxidative Stress; Phenotype; Physiological aspects; Polymorphism, Genetic; Prognosis; Promoter Regions, Genetic; Proteins; Proto-Oncogene Proteins - genetics; Proto-Oncogene Proteins - metabolism; Sequence Analysis, DNA; Sulfites; Synergistic effect; Transferases
• ISSN: 0300-8177; 1573-4919
• DOI: 10.1007/s11010-011-1103-z

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 ± 0.05 vs. 0.18 ± 0.08, P