Transforming growth factor β1 (TGFβ1) down-regulates expression and function of proliferation-inducing molecules in HPV-transformed cells

The epidemiologic association of human papillomavirus (HPV) infection with dysplasia and cervical cancer is well established. Transforming growth factor β1 (TGFβ1) is a growth inhibitory protein for epithelial cells. To examine the phenotype of HPV-transformed cells, we examined expression of TGFβ1 and a number of cellular proliferation-enhancing molecules which are known to be regulated by TGFβ1, including bcl-2 c-jun and NFκB. Previous studies had identified significant induction of TGFβ1 and concomitant downregulation of other growth stimulatory molecules in experimental papillomas. We used HPV-16 and -18 transformed cell lines. The HPV-16 transformed cells showed down-regulation of bcl-2 and NFκB as well as NFκB function upon TGFβ1 treatment. The results suggest that TGFβ1 may exert antiproliferative effects on some HPV-transformed cells by down-regulating expression and function of different proliferation-enhancing molecules. It is uncertain if this function is virus type specific and/or related to state of tumor cell progression.