Growth inhibitory effect of interferon-beta is associated with the induction of cyclin-dependent kinase inhibitor p27Kip1 in a human gastric carcinoma cell line.

The effect of IFN-beta on cell growth and the mechanism of growth modulation was examined in human gastric carcinoma cell lines. IFN-beta inhibited 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 number of those in control TMK-1 cells, whereas the induction of apoptosis was not observed in IFN-beta-treated MKN-28 cells. IFN-beta enhanced the expression of cyclin-dependent kinase inhibitor p27Kip1 at mRNA and protein levels. The increased p27Kip1 bound preferentially to CDK6. The phosphorylation level of retinoblastoma protein in TMK-1 cells was reduced by IFN-beta treatment. IFN-beta did not affect the expression of cell cycle regulators in MKN-28 cells. These results suggest that the induction of p27Kip1 by IFN-beta might confer inhibition of cell growth, leading to subsequent apoptosis in TMK-1 cells.