Inhibition of the epidermal growth factor receptor by erlotinib prevents immortalization of human cervical cells by Human Papillomavirus type 16.

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

Virology

journal_title

Virology

authors

Woodworth CD,Diefendorf LP,Jette DF,Mohammed A,Moses MA,Searleman SA,Stevens DA,Wilton KM,Mondal S

doi

10.1016/j.virol.2011.09.014

subject

Has Abstract

pub_date

2011-12-05 00:00:00

pages

19-27

issue

1

eissn

0042-6822

issn

1096-0341

pii

S0042-6822(11)00433-8

journal_volume

421

pub_type

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