title: Role of Gab2 in mammary tumorigenesis and metastasis.
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.
authors.affiliation: Cancer Center, Burnham Institute for Medical Research, La Jolla, CA 92037, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Ke
authors.forename: D
authors.initials: D
authors.lastname: Wu
authors.forename: F
authors.initials: F
authors.lastname: Princen
authors.forename: T
authors.initials: T
authors.lastname: Nguyen
authors.forename: Y
authors.initials: Y
authors.lastname: Pang
authors.forename: J
authors.initials: J
authors.lastname: Lesperance
authors.forename: W J
authors.initials: WJ
authors.lastname: Muller
authors.forename: R G
authors.initials: RG
authors.lastname: Oshima
authors.forename: G-S
authors.initials: GS
authors.lastname: Feng
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D002465:Cell Movement; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005260:Female; D018734:Genes, erbB-2; D008175:Lung Neoplasms / Q000556:secondary; D015674:Mammary Neoplasms, Animal / Q000201:enzymology / Q000235:genetics / Q000473:pathology*; D051379:Mice; D018345:Mice, Knockout; D009361:Neoplasm Invasiveness; D010750:Phosphoproteins / Q000235:genetics / Q000502:physiology*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C490894:Gab2 protein, mouse; D010750:Phosphoproteins; D048049:Extracellular Signal-Regulated MAP Kinases