Overexpression of protein kinase C-zeta (PKC-zeta) inhibits invasive and metastatic abilities of Dunning R-3327 MAT-LyLu rat prostate cancer cells.
Overexpression of protein kinase C-zeta (PKC-zeta) inhibits invasive and metastatic abilities of Dunning R-3327 MAT-LyLu rat prostate cancer cells.
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发表时间：
1996-09
期刊：
影响因子：
11.2
通讯作者：
C. T. Powell;J. Gschwend;W. Fair;N. Brittis;D. Stec;R. Huryk
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作者：
C. T. Powell;J. Gschwend;W. Fair;N. Brittis;D. Stec;R. Huryk
在此之前，我们报道了转移性Dunning R-3327大鼠前列腺癌与非转移性Dunning H前列腺癌和正常大鼠前列腺相比，蛋白激酶C(PKC)-Zeta mRNA水平显著降低(C.T.Powell等，Cell Growth&Differential，5：143-149,1994)。为了检测PKC-Zeta对侵袭性Dunning R-3327细胞系转移和侵袭能力的影响，我们建立了稳定表达活性PKC-Zeta的MAT-LyLu细胞克隆。高表达PKC-Zeta的MAT-LyLu细胞在同基因大鼠体内的致瘤性和生长速度与单独转染组和未转染组相似。然而，9个表达PKC-Zeta的细胞的独立克隆显示出比载体转染型mat-LyLu细胞克隆平均低2倍的肺转移倾向，在两种不同的方案中每只大鼠的转移分别减少约2倍和4.5倍。此外，在Boyden小室实验中，四个高表达mat-LyLu的PKC-Zeta克隆通过Matrigel的侵袭能力比三个载体转染的克隆平均降低了12倍。这些结果表明，增加PKC-Zeta的表达可以显著抑制侵袭性大鼠前列腺癌的侵袭和转移。
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.