The Mechanisms of Growth Inhibition by Transforming Growth Factor-beta1 in Cervical Carcinoma Cell Lines

Kim, M R; Kim, J W; Han, G T; Lee, J M; Jung, J K; Namkoong, S E; Kim, S J; Lee, H Y; Kim, S P

Abstract

Transforming growth factor- 1 (TGF- 1) is known to be a potent growth inhibitor of many cell types including most epithelial cells. However, the molecular mechanism of TGF- 1 action on cell growth of cervical carcinoma has not yet been elucidated. We assessed the effect of TGF- 1 on the cervical carcinoma cell lines, CUMC-3 and CUMC-6, which we estabilished in our laboratory. The results of this study were as follows: 1) TGF- 1 inhibited the growth dose-dependently at the concentration of 0.1-10 ng/ml in both cell lines. 2) DNA fragmentation and electron microscopic findings showed that TGF- 1 induced apoptosis in both cell lines 3) On northern bolt analysis, c-myc mRNA expression was suppressed by TGF- 1 in both cell lines. The inhibition of c-myc expression by TGF- 1 was more prominent in CUMC-6 than in CUMC-3. 4) Western blot analysis showed that the level of p27Kip1 protein was increased after TGF- 1 treatment in both cell lines. These results suggest that TGF- 1 induce apoptosis in two cervical carcinoma cell lines, CUMC-3 and CUMC-6, by the mechanisms involving down-regulation of c-myc gene and over-expression of p27Kip1 protein. We also suggest that CUMC-3 and CUMC-6 may be a good model for study of the complex mechanism of TGF- 1.