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| 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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| Author(s): WAYS DK, KUKOLY CA, DEVENTE J, HOOKER JL, BRYANT WO, POSEKANY KJ, FLETCHER DJ, COOK PP, PARKER PJ |
| Source: JOURNAL OF CLINICAL INVESTIGATION Volume: 95 Issue: 4 Pages: 1906-1915 Published: APR 1995 |
| Times Cited: 211 References: 42 |
| Abstract: 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.
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| Document Type: Article |
| Language: English |
| Reprint Address: WAYS, DK (reprint author), E CAROLINA UNIV, DEPT MED, ENDOCRINOL & METAB SECT, GREENVILLE, NC 27858 USA |
Addresses:
1. E CAROLINA UNIV, DEPT IMMUNOL MICROBIOL, GREENVILLE, NC 27858 USA
2. E CAROLINA UNIV, DEPT ANAT CELL BIOL, GREENVILLE, NC 27858 USA
3. IMPERIAL CANC RES FUND, PROT PHOSPHORYLAT LAB, LONDON WC2A 3PX, ENGLAND |
| Publisher: ROCKEFELLER UNIV PRESS, 222 E 70TH STREET, NEW YORK, NY 10021 |
| Subject Category: Medicine, Research & Experimental |
| IDS Number: QQ596 |
| ISSN: 0021-9738 |
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| | | | | | | | | Record from Web of Science® | | | | | | | | | |