Extracellular matrix regulates apoptosis in mammary epithelium through a control on insulin signaling.

摘要: Adherent epithelial cells require interactions with the extracellular matrix for their survival, though mechanism is ill-defined. In long term cultures of primary mammary cells, a laminin-rich basement membrane (BM) but not collagen I suppresses apoptosis, indicating that adhesion survival signals are specific in response (. J. Cell Sci. 109:631-642). We now demonstrate signal from BM mediated by integrins and requires both alpha6 beta1 subunits. addition, hormonal insulin or insulin-like growth factors, hydrocortisone prolactin, necessary to suppress cell soluble factors cooperate signaling. Insulin induced autophosphorylation its receptor whether were cultured on substrata. However, tyrosine phosphorylation substrate-1 association phosphatidylinositol 3-kinase enhanced BM, as was effector, protein kinase B. These results suggest novel matrix-dependent restriction point signaling cells. The proximal transduction event dependent matrix, activation downstream effectors BM. Since required we propose possible BM-mediated suppression apoptosis through facilitative effects