Effect of BPV1 E2-mediated inhibition of E6/E7 expression in HPV16-positive cervical carcinoma cells

Citation
Ms. Moon et al., Effect of BPV1 E2-mediated inhibition of E6/E7 expression in HPV16-positive cervical carcinoma cells, GYNECOL ONC, 80(2), 2001, pp. 168-175
Citations number
51
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Reproductive Medicine
Journal title
GYNECOLOGIC ONCOLOGY
ISSN journal
0090-8258 → ACNP
Volume
80
Issue
2
Year of publication
2001
Pages
168 - 175
Database
ISI
SICI code
0090-8258(200102)80:2<168:EOBEIO>2.0.ZU;2-A
Abstract
Objective. E6 and E7 proteins of high-risk-type human papillomavirus are ma jor etiological agents for cervical carcinomas and are continuously express ed in those cancer cells. They inhibit cell cycle control functions by inac tivating p53 and Rb proteins and also immortalize cells through the inducti on of telomerase activity. Expression of E6 and E7 genes in HeLa, an HPV18- positive cell line, has been shown to be inhibited by the E2 protein of bov ine papillomavirus (BPV1), and this resulted in the activation of the p53-m ediated growth inhibitory pathway followed by an inhibition of cell prolife ration. In this study, the effect of BPV1 E2-mediated inhibition of E6 and E7 expression was examined in HPV16-positive cervical carcinoma cell lines recently established from Korean patients. Methods. BPV1 E2 was expressed in the test cells through acute infection of an SV40-BPV1 recombinant virus. Its effect on cell proliferation was asses sed through MTT and DNA synthesis assays, and the status of factors involve d in cell cycle control was examined through Western blotting and reverse t ranscription-polymerase chain reaction. Results. BPV1 E2 expression caused a significant decrease in E6/E7 transcri ption in all three cell lines. This was accompanied by an increase in the l evels of p53 protein and activity and a decrease in the expression of Cdc25 A, a Cdk2-activating phosphatase. Concomitantly, E2F1 activity and cellular DNA synthesis capacity were significantly reduced. Conclusions, These results indicate that inhibition of E6/E7 gene expressio n in the HPV16-positive cervical carcinoma cells induces suppression in cel l proliferation by activating the growth inhibitory factors, p53 and Rb, an d also by downregulating the cell cycle stimulatory factor, Cdc25A. (C) 200 1 Academic Press.