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

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.