This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Balsitis, S. Articles by Lambert, P. F. Search for Related Content PubMed PubMed Citation Articles by Balsitis, S. Articles by Lambert, P. F.

Critical Roles for Non-pRb Targets of Human Papillomavirus Type 16 E7 in Cervical Carcinogenesis

¹ McArdle Laboratory for Cancer Research, University of Wisconsin Medical School, Madison, Wisconsin; ² Department of Biochemistry, University of Western Ontario, London, Ontario, Canada; and ³ Massachusetts General Hospital Cancer Center, Charlestown, Massachusetts

Requests for reprints: Paul F. Lambert, McArdle Laboratory for Cancer Research, University of Wisconsin Medical School, 1400 University Avenue, Madison, WI 53706. Phone: 608-262-8533; Fax: 608-262-2824; E-mail: lambert{at}oncology.wisc.edu.

High-risk human papillomaviruses (HPV) encode two oncogenes, E6 and E7, expressed in nearly all cervical cancers. In vivo, HPV-16 E7 has been shown to induce multiple phenotypes in the context of transgenic mice, including cervical cancer. E7 is a multifunctional protein known best for its ability to inactivate the tumor suppressor pRb. To determine the importance of pRb inactivation by E7 in cervical cancer, we pursued studies with genetically engineered mice. E7 expression in estrogen-treated murine cervix induced dysplasia and invasive cancers as reported previously, but targeted Rb inactivation in cervical epithelium was not sufficient to induce any cervical dysplasia or neoplasia. Furthermore, E7 induced cervical cancer formation even when the E7-pRb interaction was disrupted by the use of a knock-in mouse carrying an E7-resistant mutant Rb allele. pRb inactivation was necessary but not sufficient for E7 to overcome differentiation-induced or DNA damage–induced cell cycle arrest, and expression patterns of the E2F-responsive genes Mcm7 and cyclin E indicate that other E2F regulators besides pRb are important targets of E7. Together, these data indicate that non-pRb targets of E7 play critical roles in cervical carcinogenesis. (Cancer Res 2006; 12(18): 9393-400)

This article has been cited by other articles:

				K. Strati and P. F. Lambert Role of Rb-Dependent and Rb-Independent Functions of Papillomavirus E7 Oncogene in Head and Neck Cancer Cancer Res., December 15, 2007; 67(24): 11585 - 11593. [Abstract] [Full Text] [PDF]