Opposite effects of protein kinase C beta1 (pkcâ1) and pkcå in the metastatic potential of a breast cancer

VALERIA C. GROSSONI; LAURA B. TODARO; MARCELO G. KAZANIETZ; ELISA D. BAL DE KIER JOFFE; ALEJANDRO J. URTREGER

BREAST CANCER RESEARCH AND TREATMENT

Springer Netherlands

Año: 2009 p. 469 - 480

0167-6806

Abstract  In this paper we investigated whether protein kinase C (PKC) â1 and PKCå, members of the classical and novel PKC family, respectively, induce phenotypic alterations that could be associated with tumor progression and metastatic dissemination in a murine model of breast cancer. Stable overexpression of PKCâ1 in LM3 cells altered their ability to proliferate, adhere, and survive, and impaired their tumorigenicity and metastatic capacity. Moreover, PKCâ1 induced the re-expression of fibronectin, an extracellular matrix glycoprotein which loss has been associated with the acquisition of a transformed phenotype in different cell models, and exerted an important inhibition on proteases production, effects that probably impact on LM3 invasiveness and dissemination. Conversely, PKCå overexpression enhanced LM3 survival, anchorage-independent growth, and caused a significant increase in spontaneous lung metastasis. Our results suggest PKCâ1 functions as an inhibitory protein for tumor growth and metastasis dissemination whereas PKCå drives metastatic dissemination without affecting primary tumor growth.