Overexpression of protein kinase C-zeta (PKC-zeta) inhibits invasive and metastatic abilities of Dunning R-3327 MAT-LyLu rat prostate cancer cells.

Abstract

Previously, we reported that protein kinase C (PKC)-zeta mRNA levels are reduced markedly in metastatic Dunning R-3327 rat prostate tumors relative to the nonmetastatic Dunning H tumor and normal rat prostate (C.T. Powell et al., Cell Growth & Differ., 5: 143-149, 1994). To examine the effect of PKC-zeta on metastatic and invasive abilities of an aggressive Dunning R-3327 cell line, we generated stably transfected clones of MAT-LyLu cells that overexpress active PKC-zeta. PKC-zeta-overexpressing MAT-LyLu cells exhibited tumorigenicity and growth rates in syngeneic rats similar to those of MAT-LyLu cells transfected with vector alone or untransfected MAT-LyLu. However, nine independent clones of PKC-zeta-expressing cells exhibited an average 2-fold lower tendency to metastasize to lungs relative to vector-transfected MAT-LyLu cell clones, with about 2-fold and 4.5-fold fewer metastases per rat in two separate protocols. In addition, the ability of four PKC-zeta overexpressing MAT-LyLu clones to invade through Matrigel in a Boyden chamber assay was reduced an average of 12-fold relative to three vector-transfected clones. These results indicate that increased PKC-zeta expression can substantially suppress invasion and metastasis by an aggressive rat prostate tumor.