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ERBB-2 overexpression confers PI 3′ kinase-dependent invasion capacity on human mammary epithelial cells

2000; Springer Nature; Volume: 82; Issue: 3 Linguagem: Inglês

10.1054/bjoc.1999.0979

1532-1827

Kathleen M. Woods Ignatoski, Tomohiko Maehama, Sonja M. Markwart, Jack E. Dixon, Donna L. Livant, Stephen P. Ethier,

PI3K/AKT/mTOR signaling in cancer

Amplification and overexpression of ERBB-2 in human breast cancer is thought to play a significant role in the progression of the disease; however, its precise role in the aetiology of altered phenotypes associated with human breast cancer is unknown. We have previously shown that exogenous overexpression of ERBB-2 conferred growth factor independence on human mammary epithelial cells. In this study, we show that ERBB-2 overexpression also causes the cells to acquire other characteristics exhibited by human breast cancer cells, such as anchorage-independent growth and invasion capabilities. ERBB-2-induced invasion is dependent on fibronectin and correlates with the down-regulation of cell surface alpha4 integrin. In addition ERBB-2 co-immunoprecipitates with focal adhesion kinase (FAK) in these cells. We have also shown, by use of exogenously expressed PTEN and by treatment with the PI3'-kinase inhibitor LY294002, that ERBB-2-induced invasion is dependent on the PI3'-kinase pathway; however, PTEN does not dephosphorylate FAK in these cells.