GIULIANELLI Sebastian Jesus
congresos y reuniones científicas
PI3K/AKT PATHWAY REGULATES HORMONE SENSITIVITY AND DIFFERENTIATION IN A MOUSE MAMMARY TUMOR MODEL
MARINA RIGGIO; MARIA LAURA POLO; ALEJANDRO-COLMAN LERNER; MATIAS BLAUSTEIN; SEBASTIÁN GIULIANELLI; CLAUDIA LANARI; VIRGINIA NOVARO
Los Cocos, Cordoba. Argentina
Simposio; The First South American Spring Symposium in Signal Transduction and Molecular Medicine; 2010
Using a mouse mammary tumor model induced by medroxyprogesterone acetate (MPA) that transits through different stages of hormone dependence, we have previously reported that in the progression from hormone-dependent (HD) into a hormone-independent (HI) phenotype, the PI3K/AKT pathway becomes critical. The objective of this work was to explore if the activation of PI3K/AKT pathway in the HI tumor is responsible in regulating cellular proliferation and differentiation. We were able to generate mammary tumors in nude mice even in the absence of MPA by inoculating HD tumor cells expressing a constitutively active form of AKT1 (myristoilated AKT1). These tumors are highly differentiated and display a ductal phenotype with a cytokeratin 8 and laminin-1 positive pattern, two characteristics typical of HI tumors. Furthermore, we demonstrate that by expressing myristoilated AKT1 in a subpopulation of epithelial cells, neighboring epithelial cells respond with an increase in endogenous AKT1 levels. These results indicate that the activation of PI3K/AKT pathway is decisive in the generation of an autonomous tumor, and that paracrine signals derived from the tumor cells or its microenvironment might participate in the activation of the signaling pathway and ultimately in HI tumor growth.