Dominant negative Ras enhances lactogenic hormone-induced differentiation by blocking activation of the Raf-Mek-Erk signal transduction pathway.

ABSTRACT: Epidermal growth factor (EGF) and Ras mitogenic signal transduction pathways are frequently activated in breast carcinoma and inhibit mammary differentiation and apoptosis. HC11 mouse mammary epithelial cells, which differentiate and synthesize beta-casein following growth to confluency and stimulation with lactogenic hormones, were used to study EGF-dependent signaling during differentiation. Blocking Mek-Erk or phosphotidylinositol-3-kinase (PI-3 kinase) signaling with specific chemical inhibitors enhanced beta-casein promotor-driven luciferase activity. Because EGF stimulation of HC11 cells resulted in the activation of Ras, the effect of activated Ras (RasV12) or dominant negative (DNRasN17) on lactogen induced differentiation was examined. HC11 cell lines expressing RasV12 or DNRasN17

SUBMITTER: Cerrito MG 

PROVIDER: S-EPMC1586098 | biostudies-literature | 2004 Nov

REPOSITORIES: biostudies-literature