Atypical protein kinase C-z modulates clonogenicity, motility and secretion of proteolytic enzymes in murine mammary cells

ALEJANDRO J. URTREGER; VALERIA C. GROSSONI; MARCELO G. KAZANIETZ; ELISA D. BAL DE KIER JOFFÉ

MOLECULAR CARCINOGENESIS.

Wiley-Liss

Lugar: New York; Año: 2005 vol. 42 p. 29 - 39

0899-1987

In this paper we investigated whether protein kinase C-z (PKCz), a member of the atypical PKC family, induces phenotypic alterations associated with malignant transformation and tumor progression in mammary cells. The stable overexpression of PKCz in immortalized mammary epithelial cells (NMuMG), activates the mitogenic ERK pathway, enhanced clonal cell growth and exerts profound effects on proteases secretion. The effect on proteases expression seems to be specific for urokinase-type plasminogen activator and metalloproteinase-9 (MMP-9) since no modulation in MMP-2 and MMP-3 production could be detected. In addition, our experiments demonstrated that PKCz overexpression markedly altered the adhesive, spreading and migratory abilities of NMuMG cells. The overexpression of this enzyme was not sufficient to confer an anchorage-independent growth capacity. An extensive mutational analysis of PKCz revealed that the effects observed in NMuMG cells were strictly dependent on the kinase (catalytic) domain of the enzyme. Taken together, these results suggest that in mammary cells PKCz modulates several of the critical events involved in tumor development and dissemination through the activation of MAPK/ERK pathway.