OPPOSITE EFFECTS OF THE OVEREXPRESSION OF PROTEIN-KINASE C-GAMMA AND C-DELTA ON THE GROWTH-PROPERTIES OF HUMAN GLIOMA CELL-LINE U251 MG

In order to address the question of whether protein kinase C (PKC) is involved in the growth regulation of human glioma cells, we introduced PKC cDNA expression vectors into a human glioma cell line, U-251 MG, and established sets of stable cell clones that overexpress PKC gamma or delta. Cell clones obtained by the transfection of PKC gamma cDNA express 3.6 to 5 times more PKC activity than parental cells that express predominantly endogenous PKC alpha. These PKC gamma overexpressing cell clones show an increased rate of growth in monolayer culture, increased colony-forming efficiency on soft agarose, and increased DNA synthesis in response to epidermal growth factor and basic fibroblast growth factor. Cell clones obtained by transfection with PKC delta cDNA express 2 to 10 times more PKC than that produced endogenously. PKC delta overexpressing cells show a decreased rate of growth and decreased colony-forming efficiency. However, these PKC delta cell clones show no significant changes in responsiveness to the growth factors described above. These results clearly indicate that different PKC family members have distinct regulatory functions in cell growth and that PKC is involved in several aspects of the growth regulation of human glioma cells. (C) 1994 Academic Press, Inc.