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Expression of the invasive phenotype by MCF-7 human breast cancer cells transfected to overexpress protein kinase C-alpha or the erbB2 proto-oncogene

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Transfection of the estrogen dependent and poorly invasive MCF-7 cell line to overexpress erbB2 was reported to increase athymic nude mouse mammary fat pad tumor growth; similar PKC-alpha overexpression produced a rapidly growing and metastatic transfectant. We investigated the invasive capacities of the two transfectants in vitro, their secretion of the proteolytic enzymes metalloproteinase (MMP)-9 and -2 and urokinase-type plasminogen activator (uPA), and plasminogen activator inhibitor-1 (PAI-1), together with membrane uPA receptor (uPAR) levels as determined by ELISA. Compared with the MCF-7 cells, the erbB2 transfectant was more invasive and secreted higher levels of MMP-9 and uPA; also there was a greatly enhanced PAI-1 secretion and cellular uPAR expression. The PKC-alpha transfectant cells secreted extremely high levels of uPA and some MMP-9 and MMP-2, with an intermediate increase in uPAR; however, they were so poorly adherent that it was not possible to assess invasiveness in vitro. Thus, erbB2-overexpressing MCF-7 cells possessed several features associated with the invasive phenotype. The reportedly aggressive metastatic phenotype induced by PKC-alpha overexpression, however, was notable only for its uPA hypersecretion.
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Document Type: Research Article

Affiliations: AMER HLTH FDN,DIV NUTR & ENDOCRINOL,VALHALLA,NY 10595.

Publication date: January 1, 1997

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  • The International Journal of Oncology provides an international forum for the publication of the latest, cutting-edge research in the broad area of oncology and cancer treatment. The journal accepts original high quality works and reviews on all aspects of oncology research including carcinogenesis, metastasis, epidemiology, chemotherapy and viral oncology. Through fair and efficient peer review, the journal is dedicated to publishing top tier research in the field, offering authors rapid publication as well as high standards of copy-editing and production. The International Journal of Oncology is published on a monthly basis in both print and early online.
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