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

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Abstract
Human papillomavirus type 16 (HPV 16) 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.beta.s 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-dependnet decrease in E6 and E7 RNA expression at the transcriptional level; inhibition was dependent upon ongoing protein synthesis. TGF.beta.s 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 cells 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.

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