Oestrogen stimulates differential transcription of human papillomavirus type 16 in SiHa cervical carcinoma cells

Human papillomavirus (HPV) type 16 is highly associated with cervical cancer, but it seems that cofactors such as hormones affect its potential oncogenicity. We have analysed the HPV-16 gene expression in response to sex hormones and glucocorticoids in SiHa cells, a human cervical carcinoma cell line. An eightfold induction of HPV-16 transcripts was obtained in oestrogen-treated SiHa cells. Of the five HPV-16 transcripts detected in these cells only the two major ones, the 4.6 kb and the 4.1 kb mRNA species, were affected by oestrogen. Since the five transcripts span the E6 and E7 open reading frames of the HPV-16 genome, these results suggest that the expression of the various transcripts is differentially controlled, as oestrogen regulates only two of them. We have identified in the HPV-16 genome seven different regions with a high degree of similarity to the oestrogen-responsive element consensus sequence (GGTCANNNTGACC). These sequences are located throughout the entire HPV-16 genome. Progesterone or dexamethasone had no detectable stimulatory effect on the various transcripts of HPV-16 in SiHa cells, up to 24 h after treatment of the cells. Since the E6 and E7 open reading frames have been associated with the oncogenic potential of HPV-16, the effect of oestrogen on the transcription of these viral genes may be of biological relevance in the malignant transformation of HPV-16-infected cervical cells.