Inhibition of apoptosis in human laryngeal cancer cells by E6 and E7 oncoproteins of human papillomavirus 16
Abstract
The carcinogenesis of human papillomaviruses type 16 (HPV‐16) is mainly due to its two oncoproteins, E6 and E7. Their carcinogenic features in term of their relationship with Bcl‐2 family are still unclear. We thus aimed to analyze the expression of Bcl‐2 family members, Bcl‐2, Bax, and Bak in laryngeal cancer cells transfected with the E6 or E7 and to determine the sensitivity of these cells to apoptotic stimuli. We employed two human laryngeal cancer cell lines, UMSCC12 and UMSCC11A in this study. These two cell lines were stably transfected with HPV16 E6, E7 or empty vector, pcDNA3.1. We found that E6 and E7 inhibited apoptosis induced by TNF‐α/CHX in both UMSCC11A and UMSCC12 cells, enhanced the stability of Bcl‐2 protein and increased the degradation of Bak protein. Furthermore, it was found that HPV‐16 E7 statistically enhanced the expression of Bcl‐2 in laryngeal cancer. The alteration of Bak by E6 and E7 was not through the influence on the Bak promoter, as the luciferase assay showed that neither E6 nor E7 changed the Bak promoter activity. We conclude that the evasion of apoptosis mediated by HPV‐16 E6 and E7 is associated with increased Bcl‐2 and decreased Bak in laryngeal carcinogenesis and that the decreased level of Bak by E6 and E7 is not caused by the regulation of the Bak promoter but by reducing its protein stability. J. Cell. Biochem. 103: 1125–1143, 2008. © 2007 Wiley‐Liss, Inc.
Citing Literature
Number of times cited according to CrossRef: 11
- Takeshi Haga, Jimmy T. Efird, Sharof Tugizov, Joel M. Palefsky, Increased TNF-alpha and sTNFR2 levels are associated with high-grade anal squamous intraepithelial lesions in HIV-positive patients with low CD4 level, Papillomavirus Research, 10.1016/j.pvr.2016.11.003, 3, (1-6), (2017).
- Meysam Keshavarz, Bo Tan, Krishnan Venkatakrishnan, Cell Selective Apoptosis Induced by Polymorphic Alteration of Self-Assembled Silica Nanowebs, ACS Applied Materials & Interfaces, 10.1021/acsami.6b14836, 9, 7, (6292-6305), (2017).
- Gennaro Altamura, Annunziata Corteggio, Laura Pacini, Andrea Conte, Giovanna Maria Pierantoni, Massimo Tommasino, Rosita Accardi, Giuseppe Borzacchiello, Transforming properties of Felis catus papillomavirus type 2 E6 and E7 putative oncogenes in vitro and their transcriptional activity in feline squamous cell carcinoma in vivo, Virology, 10.1016/j.virol.2016.05.017, 496, (1-8), (2016).
- Fei Miao, Ting Lv, Yunfeng Zhang, Zheng Huang, Xiuli Wang, Hongwei Wang, Induction of apoptosis in HPV16 E7 transfected human keratinocyte by ALA-mediated photodynamic therapy, Photodiagnosis and Photodynamic Therapy, 10.1016/j.pdpdt.2015.07.004, 13, (205-210), (2016).
- Liyan Jin, Zhi-Xiang Xu, Recent advances in the study of HPV-associated carcinogenesis, Virologica Sinica, 10.1007/s12250-015-3586-3, 30, 2, (101-106), (2015).
- Steven Habbous, Vincent Pang, Wei Xu, Eitan Amir, Geoffrey Liu, Human papillomavirus and host genetic polymorphisms in carcinogenesis: A systematic review and meta-analysis, Journal of Clinical Virology, 10.1016/j.jcv.2014.07.019, 61, 2, (220-229), (2014).
- Abdullah Akpinar, Abdülhadi Cihangir Uğuz, Mustafa Nazıroğlu, Agomelatine and Duloxetine Synergistically Modulates Apoptotic Pathway by Inhibiting Oxidative Stress Triggered Intracellular Calcium Entry in Neuronal PC12 Cells: Role of TRPM2 and Voltage-Gated Calcium Channels, The Journal of Membrane Biology, 10.1007/s00232-014-9652-1, 247, 5, (451-459), (2014).
- Rodolfo Ocadiz-Delgado, Eduardo Castañeda-Saucedo, Arup K. Indra, Rogelio Hernandez-Pando, Pedro Flores-Guizar, Jose Luis Cruz-Colin, Felix Recillas-Targa, Guillermo Perez-Ishiwara, Luis Covarrubias, Patricio Gariglio, RXRα deletion and E6E7 oncogene expression are sufficient to induce cervical malignant lesions in vivo, Cancer Letters, 10.1016/j.canlet.2011.11.031, 317, 2, (226-236), (2012).
- Ann K.Y. To, George G. Chen, Ursula P.F. Chan, Caiguo Ye, Jing P. Yun, Rocky L.K. Ho, Art Tessier, Juanita L. Merchant, Paul B.S. Lai, ZBP-89 enhances Bak expression and causes apoptosis in hepatocellular carcinoma cells, Biochimica et Biophysica Acta (BBA) - Molecular Cell Research, 10.1016/j.bbamcr.2010.09.005, 1813, 1, (222-230), (2011).
- Li-zhu JIANG, Cai-feng LU, Hong-yi LU, Hong-yan CHEN, Expression of E6 oncoprotein of HPV16,cyclin D1,and human telomerase transcriptase in nasopharyngeal carcinoma tissues and its significance, Academic Journal of Second Military Medical University, 10.3724/SP.J.1008.2009.01367, 29, 12, (1367-1371), (2010).
- Han Ching Liu, George G. Chen, Alexander C. Vlantis, Michael C.F. Tong, Paul K.S. Chan, C. Andrew van Hasselt, Induction of cell cycle arrest and apoptosis by 5-fluorouracil in laryngeal cancer cells containing HPV16 E6 and E7 oncoproteins, Clinical Biochemistry, 10.1016/j.clinbiochem.2008.06.007, 41, 14-15, (1117-1125), (2008).
