GROWTH-INHIBITORY EFFECT OF INTERFERON-BETA IS ASSOCIATED WITH THE INDUCTION OF CYCLIN-DEPENDENT KINASE INHIBITOR P27(KIP1) IN A HUMAN GASTRIC-CARCINOMA CELL-LINE

The effect of IFN-beta on cell growth and the mechanism of growth modu lation was examined in human gastric carcinoma cell lines, IFN-beta in hibited the cell growth of TMK-1 cells, whereas it did not affect the growth of the other three cell lines (MKN-7, -28, and -45), The number of apoptotic cells in IFN-beta-treated TMK-1 cells was 2-fold the num ber of those in control TMK-1 cells, whereas the induction of apoptosi s was not observed in IFN-beta-treated MKN-28 cells, IFN-beta enhanced the expression of cyclin-dependent kinase inhibitor p27(Kip1) at mRNA and protein levels, The increased p27(Kip1) bound preferentially to C DK6, The phosphorylation level of retinoblastoma protein in TMK-1 cell s was reduced by IFN-beta treatment, IFN-beta did not affect the expre ssion of cell cycle regulators in MKN-28 cells, These results suggest that the induction of p27(Kip1) by IFN-beta might confer inhibition of cell growth, leading to subsequent apoptosis in TMK-1 cells.