Control of renal carcinoma TC-1 growth, cyclin/kinase and nm23 expression by IFN-gamma and TGF-beta.

To gain mechanistic insights into the growth control of renal cell carcinoma cells by IFN-gamma and TGF-beta, a recently established human renal carcinoma TC-1 cell line was treated with different concentrations of IFN-gamma and TGF-beta. Cell growth and changes in specific gene expression were evaluated. IFN-gamma exerted an antimitogenic effect on TC-1 cells, whereas TGF-beta was essentially without effect. The growth-suppressed cells had reduced expression of proliferating cell nuclear antigen (PCNA), the G2/M cell cycle transition regulatory proteins cyclin B/p34cdc2, the tumor suppressor gene pRB, and the antimetastatic gene nm23. However, levels of other cell cycle regulatory protein molecules such as cyclin D and p53 were unaffected by IFN-gamma. Thus, the antimitogenic effect of IFN-gamma may be mediated by its ability to modulate specific oncogene changes.