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

被引:81
作者
Ignatoski, KMW
Maehama, T
Markwart, SM
Dixon, JE
Livant, DL
Ethier, SP [1 ]
机构
[1] Univ Michigan, Sch Med, Dept Radiat Oncol, Ann Arbor, MI 48109 USA
[2] Univ Michigan, Sch Med, Dept Biol Chem, Ann Arbor, MI 48109 USA
[3] Univ Michigan, Sch Med, Dept Anat & Cell Biol, Ann Arbor, MI 48109 USA
关键词
ERBB2; invasion; P13 ' kinase; human breast cancer; human mammary epithelial cells;
D O I
10.1054/bjoc.1999.0979
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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-induced invasion is dependent on fibronectin and correlates with the down-regulation of cell surface alpha 4 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 PIS'-kinase inhibitor LY294002, that ERBB-2-induced invasion is dependent on the PI3'-kinase pathway; however, PTEN does not dephosphorylate FAK in these cells. (C) 2000 Cancer Research Campaign.
引用
收藏
页码:666 / 674
页数:9
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