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

Previously, we reported that protein kinase C (PKC)-ζ 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 and Differ., 5: 143-149, 1994). To examine the effect of PKC-ζ 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-ζ. PKC-ζ-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-ζ 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-ζ- 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-ζ expression can substantially suppress invasion and metastasis by an aggressive rat prostate tumor.