title: Requirement of E7 oncoprotein for viability of HeLa cells.
abstract: Most human papillomavirus (HPV)-positive cervical cancers contain integrated copies of the viral genome in their chromosomes and express the viral oncoproteins E6 and E7. A virus-encoded transcription factor, E2, is known to repress E6/E7 expression in HPV-positive cancer cells, leading to growth inhibition, which indicates that E6/E7 is required for the survival of the cells. We found that the E2-mediated growth inhibition of HeLa cells, an HPV18-positive cancer cell line, was coupled with a reduction in telomerase activity, an effect which was rescued by the complementation of E7 expression, but not E6 expression, indicating that the cell viability and the telomerase activity in HeLa cells are maintained by an E7-associated function. Analysis of E7 mutants suggested that the binding to the pRB family of pocket proteins was involved in the ability of E7 to rescue the growth potential and telomerase activity inhibited by E2 expression. We also showed that the telomerase activity upregulated by E7 expression was determined by the hTERT promoter activity, and that c-Myc upregulation caused by pRB inactivation could account for the promoter activity. The activation of p53 and consequent accumulation of p21Cip1, which were triggered by the downregulation of E6, appeared not to be essential for the E2-mediated growth arrest.
authors.affiliation: Laboratory of Gene Analysis, Department of Viral Oncology, Institute for Virus Research, Kyoto University, Sakyo-Ku, Kyoto 606-8507, Japan.
authors.forename: Akiko
authors.initials: A
authors.lastname: Nishimura
authors.forename: Tomomi
authors.initials: T
authors.lastname: Nakahara
authors.forename: Takaharu
authors.initials: T
authors.lastname: Ueno
authors.forename: Kenta
authors.initials: K
authors.lastname: Sasaki
authors.forename: Satoshi
authors.initials: S
authors.lastname: Yoshida
authors.forename: Satoru
authors.initials: S
authors.lastname: Kyo
authors.forename: Peter M
authors.initials: PM
authors.lastname: Howley
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Sakai
mesh_terms: D018797:Cell Cycle Proteins; D002470:Cell Survival; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D016259:Genes, myc / Q000235:genetics; D006367:HeLa Cells / Q000502:physiology; D006801:Humans; D009687:Nuclear Proteins / Q000378:metabolism; D009856:Oncogene Proteins, Viral / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D011401:Promoter Regions, Genetic / Q000235:genetics; D012097:Repressor Proteins / Q000378:metabolism; D019098:Telomerase / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; C054855:E2 protein, Human papillomavirus type 16; C052603:E6 protein, Human papillomavirus type 18; C052633:E7 protein, Human papillomavirus type 18; C416925:EID1 protein, human; D009687:Nuclear Proteins; D009856:Oncogene Proteins, Viral; D012097:Repressor Proteins; D019098:Telomerase