ERBB-2 overexpression confers PI 3 ' kinase-dependent invasion capacity onhuman mammary epithelial cells

Amplification and overexpression of ERBB-2 in human breast cancer is though t to play a significant role in the progression of the disease; however, it s precise role in the aetiology of altered phenotypes associated with human breast cancer is unknown. We have previously shown that exogenous overexpr ession of ERBB-2 conferred growth factor independence on human mammary epit helial cells. In this study, we show that ERBB-2 overexpression also causes the cells to acquire other characteristics exhibited by human breast cance r cells, such as anchorage-independent growth and invasion capabilities. ER BB-induced invasion is dependent on fibronectin and correlates with the dow n-regulation of cell surface alpha 4 integrin. In addition ERBB-2 co-immuno precipitates with focal adhesion kinase (FAK) in these cells. We have also shown, by use of exogenously expressed PTEN and by treatment with the PIS'- kinase inhibitor LY294002, that ERBB-2-induced invasion is dependent on the PI3'-kinase pathway; however, PTEN does not dephosphorylate FAK in these c ells. (C) 2000 Cancer Research Campaign.