Overexpression of Protein Kinase C δ Represses Expression of Proliferin in NIH3T3 Cells That Regulates Cell Proliferation

Protein kinase C (PKC) δ is known to inhibit proliferation of many cell types. In this study we found that overexpression of PKCδ reduced proliferation of NIH3T3 cells. To identify specific genes regulated by PKCδ in regulation of cell proliferation, we used differential display–polymerase chain reaction in PKCδ-overexpressing NIH3T3 cells and found that the expression of proliferin, a secreted protein known to stimulate cell proliferation, was significantly repressed. Transient transfection study indicated that the repression of proliferin expression was inversely proportional to the expression levels of PKCδ. Addition of an anti-proliferin antibody to culture medium to neutralize the secreted proliferin decreased cell proliferation in a dose-dependent manner. Our results, therefore, suggest that overexpression of PKCδ induces transcriptional repression of proliferin, thereby resulting in inhibition of cell proliferation.