Role of Gab2 in Mammary Tumorigenesis and Metastasis.
From: Cancer Center, Burnham Institute for Medical Research, La Jolla, CA 92037, USA.
Oncogene
- Publish Date: Jul 2007
- ISSN: 0950-9232
- Volume: 26
- Issue: 34
- Pages: 4951-60
- Medium: Print
- Language: English
- Citation (JAMA): Ke Y, Wu D, Princen F, et al. Role of Gab2 in Mammary Tumorigenesis and Metastasis.. Oncogene Jul 2007;26:4951-60
Abstract
Overexpression of the adaptor/scaffolding protein Gab2 has been detected in primary human breast cancer cells and cell lines, although its functional significance 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 findings 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.
Mesh Headings (Keywords): Animals, Cell Movement, Extracellular Signal-Regulated MAP Kinases, Female, Genes, erbB-2, Lung Neoplasms, Mammary Neoplasms, Animal, Mice, Mice, Knockout, Neoplasm Invasiveness, Phosphoproteins
Check for Full Text / PubMed Unique Identifier (PMID): 17310989
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