The role of the MKK6/p38 MAPK pathway in Wip1-dependent regulation of ErbB2-driven mammary gland tumorigenesis

被引：86

作者：

Demidov, O. N.

Kek, C.

Shreeram, S.

Timofeev, O.

Fornace, A. J.

Appella, E.

Bulavin, D. V.

机构：

[1] Natl Univ Singapore, Inst Mol & Cell Biol, Cell Cycle Control & Tumorigenesis Grp, Singapore 138673, Singapore

[2] NCI, Cell Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA

[3] Harvard Univ, Sch Publ Hlth, Dept Genet & Complex Dis, Boston, MA 02115 USA

来源：

ONCOGENE | 2007年 / 26卷 / 17期

基金：

美国国家卫生研究院;

关键词：

Wip1; phosphatase; p38; MAPK; MKK6; breast cancer; ErbB2; proliferation; MMTV;

D O I：

10.1038/sj.onc.1210032

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：2502 / 2506

页数：5

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