Transforming growth factor beta 1 (TGF beta 1) 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 facto r beta 1 (TGF beta 1) is a growth inhibitory protein for epithelial cells. To examine the phenotype of HPV-transformed cells, we examined expression o f TGF beta 1 and a number of cellular proliferation-enhancing molecules whi ch are known to be regulated by TGF beta 1, including bcl-2, c-jun and NFkB . Previous studies had identified significant induction of TGF beta 1 and c oncomitant downregulation of other growth stimulatory molecules in experime ntal papillomas. We used HPV-16 and -18 transformed cell lines. The HPV-16 transformed cells showed down-regulation of bcl-2 and NFkB as well as NFkB function ripen TGF beta 1 treatment. The results suggest that TGF beta 1 ma y exert antiproliferative effects on some HPV-transformed cells by down-reg ulating expression ann function of different proliferation-enhancing molecu les. It is uncertain if this function is virus type specific and/or related to state of tumor cell progression.