TRANSFORMING GROWTH-FACTOR-BETA REGULATION OF EPIDERMAL GROWTH-FACTORRECEPTOR IN ECTOCERVICAL EPITHELIAL-CELLS

Transforming growth factor beta (TGF beta) is a pluripotent modulator of cell function and an important suppressor of cervical epithelial ce ll proliferation. In the present study, we examine the effects of TGF beta 1 on the level and activity of the epidermal growth factor recept or (EGFR) in HPV-16 immortalized cervical epithelial cells. In ECE16-1 cells, increased EGFR levels are observed within 24 h after initiatio n of TGF beta 1 treatment and levels continue to increase with time. T his increase is correlated with a TGF beta 1-dependent decrease in pro liferation rate. Scatchard analysis indicates that the population of E GFR sites induced by TGF beta 1 have a low affinity for EGF (K-d = 4.0 8 nM) compared to the receptors present prior to TGF beta 1 treatment (K-d = 0.3 and 1.6 nM). TGF beta 1 treatment also reduces EGFR kinase autophosphorylation activity. Cell cycle studies indicate that TGF bet a 1-treated cells arrest in the G1 phase of the cell cycle and that re gulation of EGFR level was independent of cell cycle stage in both TGF beta 1-treated and untreated cells. However, EGFR level was related t o the G1 phase time. Parallel studies indicate that a TGF beta 1-depen dent increase in p53 level is also correlated with increased time spen t in G1. These results suggest that TGF beta 1 inhibition of ECE16-1 c ell proliferation may act both by the replacement of high affinity/hig h kinase activity EGFR sites with low affinity/low kinase activity EGF R sites and a p53-mediated cell cycle arrest. (C) 1995 Academic Press, Inc.