Adenovirus type 12 E1B 55-kilodalton oncoprotein promotes p53-mediated apoptotic response of ovarian cancer to cisplatin
- 29 March 2015
- journal article
- retracted article
- Published by Springer Science and Business Media LLC in Tumor Biology
- Vol. 36 (8), 6569-6577
- https://doi.org/10.1007/s13277-015-3351-0
Abstract
The tumor suppressor p53-mediated apoptotic response plays an important role in cisplatin resistant in ovarian cancer. The adenovirus (Ad) type 12 E1B 55-kDa protein binds to p53 and inactivates its transcriptional transactivation function. In this study, we test the hypothesis that Ad12 E1B 55-kDa oncoprotein promotes p53-mediated apoptotic response of ovarian cancer to cisplatin. First, we observed the upregulation protein level of p53 target genes in cisplatin-resistant or cisplatin-sensitive ovarian cancer by Western blotting. Second, after transfection of Ad12 E1b 55-kDa expression plasmid, the expressions of p53 target genes in A2780 cells were further enhanced. Co-IP experiment demonstrated Ad12 E1b 55 kDa associated with p53. MTT assay confirmed that the cell proliferation was enhanced after transfection, as well as the enhanced cell inhibitory rate in the presence of cisplatin. Using flow cytometry, transfection of Ad12 E1B 55-kDa protein induced apoptosis and promoted S-phase transition in proliferation. Finally, results showed that all these changes promoted by Ad12 E1b 55 kDa were attenuated by the exposure of specific inhibitor of p53 signaling, pifithrin-α. Taken together, we concluded that Ad E1B 55-kDa oncoprotein promotes p53-mediated apoptotic response of ovarian cancer to cisplatin.Keywords
This publication has 28 references indexed in Scilit:
- Cytoplasmic p21 is a potential predictor for cisplatin sensitivity in ovarian cancerBMC Cancer, 2011
- Molecular mechanisms of cisplatin resistanceOncogene, 2011
- Drug transporters of platinum-based anticancer agents and their clinical significanceDrug Resistance Updates, 2011
- Current drugs still have potential in advanced ovarian cancerNature Reviews Clinical Oncology, 2010
- Platinum–DNA Interactions and Subsequent Cellular Processes Controlling Sensitivity to Anticancer Platinum ComplexesChemistry & Biodiversity, 2010
- Pharmacogenomics of Taxane/Platinum Therapy in Ovarian CancerInternational Journal of Gynecologic Cancer, 2009
- Molecular pathogenesis and therapeutic targets in epithelial ovarian cancerJournal of Cellular Biochemistry, 2007
- Adenovirus E1B 55-Kilodalton Oncoprotein Binds to Daxxand Eliminates Enhancement of p53-Dependent Transcription byDaxxJournal of Virology, 2003
- Intraperitoneal cisplatin‐based chemotherapy vs. intravenous cisplatin‐based chemotherapy for stage III optimally cytoreduced epithelial ovarian cancerInternational Journal of Gynecology & Obstetrics, 2001
- p53 in growth control and neoplasiaBiochimica et Biophysica Acta (BBA) - Reviews on Cancer, 1996