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

C D Woodworth, V Notario, J A DiPaolo
1990 Journal of Virology  
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 (TGFI3s 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 timeand dose-dependent decrease in E6 and E7 RNA levels
more » ... nd E7 RNA levels and was accompanied by cessation of cell proliferation. TGF,s 1 and 2 inhibited HPV16 RNA expression at the transcriptional level; inhibition was dependent upon ongoing protein synthesis. TGFj3s 1 and 2 also induced a sixto sevenfold increase in TGFi 1 RNA. Cells became partially resistant to the inhibitory effects of TGF,3 1 on cell growth and HPV early gene expression after prolonged cultivation in vitro or after malignant transformation. Thus, TGF( 1 may function as an autocrine regulator of HPV gene expression in infected genital epithelial cells.
doi:10.1128/jvi.64.10.4767-4775.1990 fatcat:7e2zwyaau5fyjpuc643iskrwyq