CONVERSION OF NORMAL HUMAN ORAL KERATINOCYTES TO TUMORIGENIC CELLS ISASSOCIATED WITH THE ACQUISITION OF RESISTANCE TO TGF-BETA

Normal human epithelial cells cannot proliferate and undergo apoptosis in the presence of transforming growth factor-beta (TGF-beta) in vitr o, but many human epidermoid cancer cells are resistant to TGF-beta. R esistance to TGF-beta may thus, in part, be responsible for uncontroll ed proliferation of cancer cells. Though detailed mechanisms for the r esistance of cancer cells to TGF-beta remain unknown, resistance may b e due to decreased expression of TGF-beta receptors from cancer cells. To investigate this possibility, we determined the expression of TGF- beta and type II TGF-beta receptor in primary normal human oral kerati nocytes (NHOK), human papillomavirus-immortalized human oral keratinoc ytes (HOK-16B) and two tumor cell lines derived from HOK-16B (CTHOK-16 B-BaP and CTHOK-16B-DMBA). Our results show that (1) the cellular and secretory TGF-beta levels in immortalized and tumor cells were notably lower than in NHOK and (2) the level of type II TGF-beta receptor of the tested cells was similar to each other. Taken together, the conver sion of NHOK to tumorigenic cells may, in part, be due to the acquisit ion of NHOK resistance to TGF-beta through underexpression of this cyt okine.