MAP kinase pathway signalling is essential for extracellular matrix determined mammary epithelial cell survival

Mammary epithelial cells in primary cell culture require both growth factor s and specific extracellular matrix (ECM)attachment for survival. Here we d emonstrate for the first time that inhibition of the ECM-induced Erk 1/Erk 2 (p42/44 MAPK) pathway, by PD 98059, leads to apoptosis in these cells. As sociated with this cell death is a possible compensatory signalling through the p38 MAP kinase pathway the inhibition of which, by SE 203580, leads to a more rapid onset of apoptosis. This provides evidence for a hitherto und escribed Erk 1/Erk 2 to p38 MAP kinase pathway 'cross-talk' that is essenti al for the survival of these cells. The cell death associated with inhibiti on of these two MAP kinase pathways however, occurred in the presence of in sulin that activates the, classical PI-3 kinase-dependent Akt/PKB survival signals and Akt phosphorylation. Cell death induced by inhibition of the MA P kinase pathways did not affect Akt phosphorylation and may, thus, be inde pendent of PI-3 kinase signalling.