Indian Journal of Medical and Paediatric Oncology, Table of Contents CC BY-NC-ND 4.0 · Indian J Med Paediatr Oncol 2015; 36(01): 49-54DOI: 10.4103/0971-5851.151784 ORIGINAL ARTICLE Role of CTCF poly(ADP-Ribosyl)ation in the regulation of apoptosis in breast cancer cells Bhooma Venkatraman Australian School of Advanced Medicine, Macquarie University, Sydney, Australia , Elena Klenova School of Biological Sciences, University of Essex, United Kingdom › Author Affiliations Recommend Article Abstract PDF Download Abstract Introduction: CTCF is a candidate tumor suppressor gene encoding a multifunctional transcription factor. CTCF function is controlled by posttranslational modification and interaction with other proteins. Research findings suggested that CTCF function can be regulated by poly(ADP-ribosyl)ation (PARlation) and has specific anti-apoptotic function in breast cancer cells. The aim of this study is to assess the effect of CTCF-wild type (WT) and CTCF complete mutant, which is deficient of PARlation in regulating apoptosis in breast cancer cells. Materials and Methods: The effect of CTCF-WT and CTCF complete mutant was expressed in breast cancer cell-lines by DNA-mediated transfection technique monitored by enhanced green fluorescent protein fluorescence. Evaluation of apoptotic cell death was carried out with immunohistochemical staining using 4′-6′-diamino-2 phenylindole and scoring by fluorescent microscopy. Results: CTCF-WT supports survival of breast cancer cells and was observed that CTCF complete mutant interferes with the functions of the CTCF-WT and there was a considerable apoptotic cell death in the breast cancer cell lines such as MDA-MB-435, CAMA-1 and MCF-7. Conclusion: The study enlighten CTCF as a "Biological Marker" for breast cancer and the role of CTCF PARlation may be involved in breast carcinogenesis. Keywords Keywords4′-6′-diamino-2 phenylindole - CTCF complete mutant - CTCF-wild type - poly(ADP-ribosyl)ation - transfection PDF (1045 kb) References References 1 Klenova E, Ohlsson R. Poly (ADP-ribosyl)ation and epigenetics. Is CTCF PARt of the plot? Cell Cycle 2005;4:96-101. 2 Nakahashi H, Kwon KR, Resch W, Vian L, Dose M, Stavreva D, et al. A genome-wide map of CTCF multivalency redefines the CTCF code. Cell Rep 2013;3:1678-89. 3 Kanduri C, Pant V, Loukinov D, Pugacheva E, Qi CF, Wolffe A, et al. Functional association of CTCF with the insulator upstream of the H19 gene is parent of origin-specific and methylation-sensitive. Curr Biol 2000;10:853-6. 4 Yu W, Ginjala V, Pant V, Chernukhin I, Whitehead J, Docquier F, et al. Poly (ADP-ribosyl)ation regulates CTCF-dependent chromatin insulation. Nat Genet 2004;36:1105-10. 5 Filippova GN, Qi CF, Ulmer JE, Moore JM, Ward MD, Hu YJ, et al. Tumor-associated zinc finger mutations in the CTCF transcription factor selectively alter TTS DNA-binding specificity. Cancer Res 2002;62:48-52. 6 Smith S. The world according to PARP. Trends Biochem Sci 2001;26:174-9. 7 Klenova EM, Morse HC 3 rd , Ohlsson R, Lobanenkov VV. The novel BORIS + CTCF gene family is uniquely involved in the epigenetics of normal biology and cancer. Semin Cancer Biol 2002;12:399-414. 8 Studzinski GP. Cell Growth and Apoptosis. 1 st ed. Oxford: IRC Press; 1995. 9 Mandal M, Kumar R. Bcl-2 expression regulates sodium butyrate-induced apoptosis in human MCF-7 breast cancer cells. Cell Death Differ 1996;7:311-8. 10 Chopin V, Toillon RA, Jouy N, Le Bourhis X. Sodium butyrate induces P53-independent, Fas-mediated apoptosis in MCF-7 human breast cancer cells. Br J Pharmacol 2002;135:79-86. 11 Martelli AM, Zweyer M, Ochs RL, Tazzari PL, Tabellini G, Narducci P, et al. Nuclear apoptotic changes: An overview. J Cell Biochem 2001;82:634-46. 12 Vousden KH, Lu X. Live or let die: The cell′s response to p53. Nat Rev Cancer 2002;2:594-604. 13 Docquier F, Farrar D, D′Arcy V, Chernukhin I, Robinson AF, Loukinov D, et al. Heightened expression of CTCF in breast cancer cells is associated with resistance to apoptosis. Cancer Res 2005;65:5112-22. 14 Guastafierro T, Cecchinelli B, Zampieri M, Reale A, Riggio G, Sthandier O, et al. CCCTC-binding factor activates PARP-1 affecting DNA methylation machinery. J Biol Chem 2008;283:21873-80. 15 Li Y, Huang W, Niu L, Umbach DM, Covo S, Li L. Characterization of constitutive CTCF/cohesin loci: A possible role in establishing topological domains in mammalian genomes. BMC Genomics 2013;14:553.
