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

Oncogene volume 26, pages 2502–2506 (2007)Cite this article

Abstract

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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Authors and Affiliations

  1. Cell Cycle Control and Tumorigenesis Group, Institute of Molecular and Cell Biology, Proteos, Singapore

    O N Demidov, C Kek, S Shreeram, O Timofeev & D V Bulavin

  2. Laboratory of Cell Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA

    E Appella

  3. Department of Genetics and Complex Diseases, Harvard School Of Public Health, Boston, MA, USA

    A J Fornace

Authors
  1. O N Demidov
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  2. C Kek
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  3. S Shreeram
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  4. O Timofeev
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  5. A J Fornace
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  6. E Appella
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  7. D V Bulavin
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Correspondence to D V Bulavin.

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Demidov, O., Kek, C., Shreeram, S. et al. The role of the MKK6/p38 MAPK pathway in Wip1-dependent regulation of ErbB2-driven mammary gland tumorigenesis. Oncogene 26, 2502–2506 (2007). https://doi.org/10.1038/sj.onc.1210032

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  • DOI: https://doi.org/10.1038/sj.onc.1210032

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