This Article 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 Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Woodworth, C D Articles by DiPaolo, J A Search for Related Content PubMed PubMed Citation Articles by Woodworth, C D Articles by DiPaolo, J A

Transforming growth factors beta 1 and 2 transcriptionally regulate human papillomavirus (HPV) type 16 early gene expression in HPV-immortalized human genital epithelial cells.

Laboratory of Biology, National Cancer Institute, Bethesda, Maryland 20892.

ABSTRACT

Human papillomavirus type 16 (HPV16) early proteins E6 and E7 have been implicated in maintenance of the malignant phenotype in cervical cancer. Transforming growth factors beta one and two (TGF betas 1 and 2), polypeptides that regulate cellular growth and differentiation, reversibly inhibited expression of the HPV16 E6 and E7 genes in several immortal genital epithelial cell lines. Loss of E6 and E7 protein expression followed a dramatic time- and dose-dependent decrease in E6 and E7 RNA levels and was accompanied by cessation of cell proliferation. TGF betas 1 and 2 inhibited HPV16 RNA expression at the transcriptional level; inhibition was dependent upon ongoing protein synthesis. TGF betas 1 and 2 also induced a six- to sevenfold increase in TGF beta 1 RNA. Cells became partially resistant to the inhibitory effects of TGF beta 1 on cell growth and HPV early gene expression after prolonged cultivation in vitro or after malignant transformation. Thus, TGF beta 1 may function as an autocrine regulator of HPV gene expression in infected genital epithelial cells.

This article has been cited by other articles:

• Smoak, K., Cidlowski, J. A. (2006). Glucocorticoids Regulate Tristetraprolin Synthesis and Posttranscriptionally Regulate Tumor Necrosis Factor Alpha Inflammatory Signaling. Mol. Cell. Biol. 26: 9126-9135 [Abstract] [Full Text]  
• Palefsky, J. (2006). Biology of HPV in HIV Infection. Adv. Dent. Res. 19: 99-105 [Abstract] [Full Text]  
• Baldwin, A., Pirisi, L., Creek, K. E. (2004). NFI-Ski Interactions Mediate Transforming Growth Factor {beta} Modulation of Human Papillomavirus Type 16 Early Gene Expression. J. Virol. 78: 3953-3964 [Abstract] [Full Text]  
• Scott, M., Nakagawa, M., Moscicki, A.-B. (2001). Cell-Mediated Immune Response to Human Papillomavirus Infection. CVI 8: 209-220 [Full Text]  
• Nees, M., Geoghegan, J. M., Munson, P., Prabhu, V., Liu, Y., Androphy, E., Woodworth, C. D. (2000). Human Papillomavirus Type 16 E6 and E7 Proteins Inhibit Differentiation-dependent Expression of Transforming Growth Factor-{beta}2 in Cervical Keratinocytes. Cancer Res. 60: 4289-4298 [Abstract] [Full Text]  
• Hausen, H. z. (2000). Papillomaviruses Causing Cancer: Evasion From Host-Cell Control in Early Events in Carcinogenesis. JNCI J Natl Cancer Inst 92: 690-698 [Abstract] [Full Text]  
• Xu, X.-C., Mitchell, M. F., Silva, E., Jetten, A., Lotan, R. (1999). Decreased Expression of Retinoic Acid Receptors, Transforming Growth Factor {beta}, Involucrin, and Cornifin in Cervical Intraepithelial Neoplasia. Clin. Cancer Res. 5: 1503-1508 [Abstract] [Full Text]  
• zur Hausen, H (1991). Viruses in human cancers. Science 254: 1167-1173 [Abstract]