Involvement of the TGF-β and mTOR/p70S6Kinase pathways in the transformation process induced by v-ErbA

Abstract v-ErbA is the oncogenic form of TRα/c-ErbA which transforms chicken erythrocytic progenitors by blocking differentiation. The oncogenic property of v-ErbA has been correlated with its ability to antagonize ligand-dependent gene activation by TRα/c-ErbA and retinoic acid receptors. Nevertheless, its cytoplasmic retention suggests that v-ErbA could interfere with intracellular signaling pathways. We demonstrate that only the transforming form of v-ErbA confers to chicken erythroid progenitors a TGF-β independency and induces an activation of the mTOR/p70S6K pathway. In these cells, TGF-β and mTOR/p70S6K pathways regulate the expression of a known target gene of v-ErbA, band3 . This is the first demonstration that v-ErbA is able to modulate specifically some signaling pathways leading to changes in the expression level of a gene involved in transformation.