Effects of TGF-beta onthe HPC-16-induced Neoplastic Transformation of Human Cells

Park, Il Soo; Lee, Yoon Soon; Lee, Chun Hee; Kim, Sam Sik; Kim, Dae Han; Kim, Kwang Soo; Yang, Jae Ho

Abstract

Human epithelial cell line immortalized with Ad12-SV40 hybrid virus was transfected with plasmid containing HPV-16 gene. Among these clones, clone-3 and clone-6 showed neoplastic transformation properties of contact inhibition, anchorage independence and cellular adhesion after 7 subcultures. The results suggest that SV40 gene in the immortalized human cell system be in concert with HPV-16 in the process of neoplastic transformation of human cells. While TGF-Beta1(5ng/ml) inhibited growth of contml cells and clone-1 cells which did not show transformation, there was no significant change on the growth of clone-3 cells with transformation properties. When transcriptional level of fibronectin on control cells and clone-3 cells were analyzed with northern blot technique, transcription of fibronectin an clone-3 cells were higher, as compared with control cells. RNA hybridization techniques were performed to compare trasnscriptional levels of TGF-Beta1 between control cells and clone-3 cells. RNA level on clone-3 cells with transformation properties was higher than on control cells. These studies indicate that TGF-Beta1 is associated with increases of fibronectin, which may lend to changes of TGF-Beta receptor and loss of its inhibitory action on the transformed cells. Thus, it seems that loss of inhibitory action of TGF-Beta which is mediated by changes of fibronectin may account for a possible mechanism of action in the HPV-16 induced transformation of human cells.