EXPRESSION OF P16(INK4A) SUPPRESSES THE UNBOUNDED AND ANCHORAGE-INDEPENDENT GROWTH OF A GLIOBLASTOMA CELL-LINE THAT LACKS P16(INK4A)

p16(INK4a) is a inhibitory protein of Cyclin-dependent kinase 4 (Cdk4) . p16 negatively regulates the cell cycle progression from G1 to S pha se. Functional pie is absent from many human cancers, as well as from many established lines of tumor cells. However, it is not clear whethe r expression of p16 in p16-deficient tumor cells can suppress their an chorage-independent growth. Therefore, we introduced a cDNA for p16(IN K4a) into the human glioblastoma cell line T98G, which lacks a gene fo r p16(INK4a). We isolated several clones that stably expressed various amounts of pie protein. The doubling time of the various clones was g enerally prolonged. Clones with high-level expression of p16 protein h ad characteristics of restricted growth, such as contact inhibition, w hile the parental T98G cells had no such characteristics. Furthermore, the efficiency of colony formation in soft agar was dramatically decr eased in the case of cells that expressed exogenous pie. Our observati ons suggest that the expression of pie protein restricts the unbounded growth and the anchorage-independent growth of tumor cells. (C) 1997 Academic Press.