title: ERBB-2 overexpression confers PI 3' kinase-dependent invasion capacity on human mammary epithelial cells.
abstract: 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.
authors.affiliation: Department of Radiation Oncology, University of Michigan Medical School, Ann Arbor 48109-0616, USA.
authors.forename: K M
authors.initials: KM
authors.lastname: Ignatoski
authors.forename: T
authors.initials: T
authors.lastname: Maehama
authors.forename: S M
authors.initials: SM
authors.lastname: Markwart
authors.forename: J E
authors.initials: JE
authors.lastname: Dixon
authors.forename: D L
authors.initials: DL
authors.lastname: Livant
authors.forename: S P
authors.initials: SP
authors.lastname: Ethier
mesh_terms: D001940:Breast / Q000166:cytology / Q000201:enzymology / Q000378:metabolism*; D001943:Breast Neoplasms / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D002455:Cell Division; D002470:Cell Survival; D018734:Genes, erbB-2; D006801:Humans; D009361:Neoplasm Invasiveness / Q000235:genetics*; D010641:Phenotype; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D019869:Phosphatidylinositol 3-Kinases