MCF-7 BREAST-CANCER CELLS TRANSFECTED WITH PROTEIN-KINASE C-ALPHA EXHIBIT ALTERED EXPRESSION OF OTHER PROTEIN-KINASE-C ISOFORMS AND DISPLAY A MORE AGGRESSIVE NEOPLASTIC PHENOTYPE
MCF-7 BREAST-CANCER CELLS TRANSFECTED WITH PROTEIN-KINASE C-ALPHA EXHIBIT ALTERED EXPRESSION OF OTHER PROTEIN-KINASE-C ISOFORMS AND DISPLAY A MORE AGGRESSIVE NEOPLASTIC PHENOTYPE
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DOI：
10.1172/jci117872
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发表时间：
1995-04-01
影响因子：
15.9
通讯作者：
PARKER, PJ
中科院分区：
文献类型：
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作者：
WAYS, DK;KUKOLY, CA;PARKER, PJ
乳腺癌恶性组织中蛋白激酶C(PKC)活性的升高与乳腺癌细胞系中更具侵袭性的表型表达呈正相关，提示该信号转导通路在乳腺癌的发生和发展中起作用。为了研究PKC在乳腺癌发生发展中的作用，将PKC-α基因导入人MCF-7乳腺癌细胞，分离到一组稳定高表达PKC-α的异源细胞(MCF-7-PKC-α)。与亲本或载体转染的MCF-7细胞相比，MCF-7-PKC-α细胞表达的PKC-α水平高5倍。MCF-7-PKC-α细胞的内源性PKC-β表达显著增加，新的Delta和ETA-PKC亚型表达减少。MCF-7-PKC-α细胞在裸鼠体内表现出更高的增殖率、不依赖于锚定的生长、明显的形态改变，包括失去上皮样外观，以及更高的致瘤性。MCF-7-PKC-α细胞的雌激素受体表达和雌激素依赖基因表达均显著降低，提示PKC通路可能参与调控乳腺癌向更具侵袭性的肿瘤过程发展。
Increased protein kinase C (PKC) activity in malignant breast tissue and positive correlations between PKC activity and expression of a more aggressive phenotype in breast cancer cell lines suggest a role for this signal transduction pathway in the pathogenesis and/or progression of breast cancer, To examine the role of PKC in the progression of breast cancer, human MCF-7 breast cancer cells were transfected with PKC-alpha and a group of heterogenous cells stably overexpressing PKC-alpha were isolated (MCF-7-PKC-alpha). MCF-7-PKC-alpha cells expressed fivefold higher levels of PKC-alpha as compared to parental or vector-transfected MCF-7 cells. MCF-7-PKC-alpha cells also displayed a substantial increase in endogenous expression of PKC-beta and decreases in expression of the novel delta- and eta-PKC isoforms.MCF-7-PKC-alpha cells displayed an enhanced proliferative rate, anchorage-independent growth, dramatic morphologic alterations including loss of an epithelioid appearance, and increased tumorigenicity in nude mice. MCF-7-PKC-alpha cells exhibited a significant reduction in estrogen receptor expression and decreases in estrogen-dependent gene expression, These findings suggest that the PKC pathway may modulate progression of breast cancer to a more aggressive neoplastic process.