期刊
ONCOGENE
卷 26, 期 17, 页码 2502-2506出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/sj.onc.1210032
关键词
Wip1 phosphatase; p38 MAPK; MKK6; breast cancer; ErbB2; proliferation; MMTV
There is increasing evidence for the role of wild-type p53 induced phosphatase 1( Wip1) phosphatase in the regulation of tumorigenesis. To evaluate Wip1 as a breast cancer oncogene, we generated a mouse strain with targeted expression of Wip1 to the breast epithelium. We found that these mice are prone to cancer when intercrossed with transgenics expressing the ErbB2 oncogene but not conditional knockouts for Brca2. This tumor-prone phenotype of Wip1 is fully eliminated through attenuation of proliferation by activating the MKK6/p38 mitogen-activated protein kinases ( MAPK) cascade in mice bearing a constitutively active form of MKK6. We propose that Wip1 phosphatase operates within the MKK6/p38 MAPK signaling pathway to promote ErbB2-driven mammary gland tumorigenesis.
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