Abstract:
:The Human Papillomavirus type-16 (HPV-16) E6 and E7 oncogenes are selectively retained and expressed in cervical carcinomas, and expression of E6 and E7 is sufficient to immortalize human cervical epithelial cells. Expression of the epidermal growth factor receptor (EGFR) is often increased in cervical dysplasia and carcinoma, and HPV oncoproteins stimulate cell growth via the EGFR pathway. We found that erlotinib, a specific inhibitor of EGFR tyrosine kinase activity, prevented immortalization of cultured human cervical epithelial cells by the complete HPV-16 genome or the E6/E7 oncogenes. Erlotinib stimulated apoptosis in cells that expressed HPV-16 E6/E7 proteins and induced senescence in a subpopulation of cells that did not undergo apoptosis. Since immortalization by HPV E6/E7 is an important early event in cervical carcinogenesis, the EGFR is a potential target for chemoprevention or therapy in women who have a high risk for cervical cancer.
journal_name
Virologyjournal_title
Virologyauthors
Woodworth CD,Diefendorf LP,Jette DF,Mohammed A,Moses MA,Searleman SA,Stevens DA,Wilton KM,Mondal Sdoi
10.1016/j.virol.2011.09.014subject
Has Abstractpub_date
2011-12-05 00:00:00pages
19-27issue
1eissn
0042-6822issn
1096-0341pii
S0042-6822(11)00433-8journal_volume
421pub_type
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