This Article Full Text Full Text (PDF) Correction (v69,p3721) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend 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 Holland, D. Articles by Hoppe-Seyler, F. Search for Related Content PubMed PubMed Citation Articles by Holland, D. Articles by Hoppe-Seyler, F.

Activation of the Enhancer of Zeste Homologue 2 Gene by the Human Papillomavirus E7 Oncoprotein

¹ Molecular Therapy of Virus-Associated Cancers (F065), German Cancer Research Center, Heidelberg, Germany and ² Gynäkologische Molekularbiologie, Frauenklinik der FSU Jena, Jena, Germany

Requests for reprints: Felix Hoppe-Seyler, Deutsches Krebsforschungszentrum, Molekulare Therapie Virus-assoziierter Tumore (F065), Im Neuenheimer Feld 242, D-69120 Heidelberg, Germany. Phone: 49-6221-424872; Fax: 49-6221-424852; E-mail: hoppe-seyler{at}dkfz.de.

Key Words: human papillomavirus • cervical cancer • enhancer of zeste homologue 2 • tumor virus

The malignant phenotype of human papillomavirus (HPV)-positive cancer cells is maintained by the activity of the viral E6 and E7 genes. Here, we identified the polycomb group gene enhancer of zeste homologue 2 (EZH2) as a novel downstream target for the viral oncogenes in HPV-transformed cells. EZH2 expression was activated by HPV16 E7 at the transcriptional level via E7-mediated release of E2F from pocket proteins. RNA interference analyses showed that continuous EZH2 expression is required for the proliferation of HPV-positive tumor cells by stimulating cell cycle progression at the G₁-S boundary. In addition to its growth-promoting activity, EZH2 also contributed to the apoptotic resistance of cervical cancer cells. Furthermore, we found that HPV-positive dysplastic and tumorigenic cervical lesions were characterized by high levels of EZH2 protein in vivo. We conclude that the E7 target gene EZH2 is a major determinant for the proliferation of HPV-positive cancer cells and contributes to their apoptotic resistance. Moreover, EZH2 may serve as a novel therapeutic target for the treatment of cervical cancer. [Cancer Res 2008;68(23):9964–72]

This article has been cited by other articles:

				Correction: Article on Activation of EZH2 by HPV Cancer Res., April 15, 2009; 69(8): 3721 - 3721. [Full Text] [PDF]