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
| Autor: | Cynthia A. Kukoly, Paul P. Cook, Winifred O. Bryant, James E. deVente, Peter J. Parker, D. K. Ways, J. Hooker, Karla J. Posekany, Donald J. Fletcher |
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| Rok vydání: | 1995 |
| Předmět: |
Protein Kinase C-alpha
Blotting Western Mice Nude Estrogen receptor Breast Neoplasms Biology Transfection Mice Breast cancer Gene expression Cell Adhesion medicine Animals Humans Neoplasm Invasiveness Neoplasm Metastasis skin and connective tissue diseases Protein Kinase C Protein kinase C Mice Inbred BALB C Cell Cycle Mammary Neoplasms Experimental General Medicine Cell cycle Blotting Northern medicine.disease Recombinant Proteins Isoenzymes Phenotype MCF-7 Cancer research Female Signal transduction Research Article |
| Zdroj: | Journal of Clinical Investigation. 95:1906-1915 |
| ISSN: | 0021-9738 |
| DOI: | 10.1172/jci117872 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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