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

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.

• Authors: O N Demidov, C Kek, S Shreeram, O Timofeev, A J Fornace, E Appella, D V Bulavin
• Journal: Oncogene (Oncogene) Vol. 26 Issue 17 Pg. 2502-6 (Apr 12 2007) ISSN: 0950-9232 [Print] England
• PMID: 17016428 (Publication Type: Journal Article)

Chemical References

• Neoplasm Proteins
• Receptor, ErbB-2
• p38 Mitogen-Activated Protein Kinases
• MAP Kinase Kinase 6
• Map2k6 protein, mouse
• PPM1D protein, human
• Phosphoprotein Phosphatases
• Ppm1d protein, mouse
• Protein Phosphatase 1
• Protein Phosphatase 2C

Topics

• Animals
• Female
• Humans
• MAP Kinase Kinase 6 (physiology)
• MAP Kinase Signaling System (genetics)
• Mammary Neoplasms, Experimental (enzymology, genetics, metabolism, pathology)
• Mice
• Mice, Knockout
• Mice, Transgenic
• Neoplasm Proteins (deficiency, genetics, physiology)
• Phosphoprotein Phosphatases (deficiency, genetics, physiology)
• Protein Phosphatase 1
• Protein Phosphatase 2C
• Receptor, ErbB-2 (physiology)
• p38 Mitogen-Activated Protein Kinases (physiology)