Journal
ONCOGENE
Volume 26, Issue 34, Pages 4951-4960Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/sj.onc.1210315
Keywords
Gab2; mammary tumor; metastasis; signal transduction; cell migration; scaffolding protein
Funding
- NCI NIH HHS [CA102583, CA78606] Funding Source: Medline
- NHLBI NIH HHS [HL66208] Funding Source: Medline
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Overexpression of the adaptor/scaffolding protein Gab2 has been detected in primary human breast cancer cells and cell lines, although its functional signifi. cance in breast carcinogenesis is not fully understood. Here, we show a requirement for Gab2 in promoting mammary tumor metastasis. Although Gab2 expression levels were elevated in mammary tumors induced by the Neu (ErbB-2) oncogene, homozygous deletion of Gab2 in mice had only a modest effect on the initiation of Neu-induced mammary tumors. Notably, ablation of Gab2 severely suppressed lung metastasis. Gab2-deficient cancer cells displayed normal Akt activities, and their proliferative rate in vitro was similar to control cells. However, Gab2(-/-) cancer cells exhibited decreased migration and impaired Erk activation, and the defects were rescued by re-introduction of Gab2 into Gab2(-/-) cells. These. ndings suggest that although Gab2 overexpression may confer growth advantage to tumor cells, the functional requirement for Gab2 in mammary tumor initiation/growth may be dispensable, and that Gab2 may have a prominent role in promoting mammary tumor metastasis.
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