RGD Reference Report - The mitogen-activated protein kinase kinase 4 has a pro-oncogenic role in skin cancer. - Rat Genome Database

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The mitogen-activated protein kinase kinase 4 has a pro-oncogenic role in skin cancer.

Authors: Finegan, KG  Tournier, C 
Citation: Finegan KG and Tournier C, Cancer Res. 2010 Jul 15;70(14):5797-806. doi: 10.1158/0008-5472.CAN-09-3669. Epub 2010 Jul 7.
RGD ID: 7495823
Pubmed: PMID:20610622   (View Abstract at PubMed)
PMCID: PMC2906708   (View Article at PubMed Central)
DOI: DOI:10.1158/0008-5472.CAN-09-3669   (Journal Full-text)

The mitogen-activated protein kinase (MAPK) kinase 4 (MKK4) is a nonredundant component of stress-activated MAPK signaling modules. Its function in tumorigenesis remains highly controversial with some studies indicating that MKK4 is a tumor suppressor, whereas others have reported a pro-oncogenic role. To clarify the role of MKK4 in cancer, we have created a novel mouse model to test the effect of the specific loss of MKK4 in the epidermis on the formation of papillomas caused by activated ras mutation. We have discovered that skin-specific MKK4-deficient mice are resistant to carcinogen-induced tumorigenesis. One mechanism by which MKK4 promotes cell proliferation and the formation of tumors is by increasing epidermal growth factor receptor expression through the c-Jun NH(2)-terminal protein kinase/c-Jun signaling pathway. Together, our results provide the first genetic demonstration that MKK4 is essential to mediate the oncogenic effect of Ras in vivo, thereby validating MKK4 as a potential drug target for cancer therapy.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
papilloma  ISOMap2k4 (Mus musculus)7495823; 7495823 RGD 
papilloma  IMP 7495823 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Map2k4  (mitogen activated protein kinase kinase 4)

Genes (Mus musculus)
Map2k4  (mitogen-activated protein kinase kinase 4)

Genes (Homo sapiens)
MAP2K4  (mitogen-activated protein kinase kinase 4)


Additional Information