Overexpression of protein kinase C-zeta (PKC-zeta) inhibits invasive and metastatic abilities of Dunning R-3327 MAT-LyLu rat prostate cancer cells.
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.
Powell
C T
CT
Urological Oncology Research Laboratory, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA. powellt@mskcc.org
Gschwend
J E
JE
Fair
W R
WR
Brittis
N J
NJ
Stec
D
D
Huryk
R
R
D000818:Animals; D001358:Avian Sarcoma Viruses; D002460:Cell Line; D003001:Cloning, Molecular; D003094:Collagen; D004338:Drug Combinations; D015870:Gene Expression; D005822:Genetic Vectors; D007797:Laminin; D008297:Male; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D011467:Prostate / Q000201:enzymology; D011471:Prostatic Neoplasms / Q000201:enzymology* / Q000473:pathology*; D011493:Protein Kinase C / Q000096:biosynthesis*; D011509:Proteoglycans; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011994:Recombinant Proteins / Q000096:biosynthesis; D014162:Transfection; D014185:Transplantation, Isogeneic; D014407:Tumor Cells, Cultured; D000099221:Protein Kinase C zeta
D003094:Collagen; D004338:Drug Combinations; D007797:Laminin; D011493:Protein Kinase C; D011509:Proteoglycans; D012333:RNA, Messenger; D011994:Recombinant Proteins; D000099221:Protein Kinase C zeta; C059485:matrigel