Unknown

Dataset Information

0

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


ABSTRACT: 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.

SUBMITTER: Finegan KG 

PROVIDER: S-EPMC2906708 | biostudies-literature | 2010 Jul

REPOSITORIES: biostudies-literature

altmetric image

Publications

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

Finegan Katherine G KG   Tournier Cathy C  

Cancer research 20100707 14


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 m  ...[more]

Similar Datasets

| S-EPMC8533050 | biostudies-literature
| S-EPMC5625047 | biostudies-literature
| S-EPMC124141 | biostudies-literature
2022-07-13 | GSE201823 | GEO
| S-EPMC7072904 | biostudies-literature
| S-EPMC8799529 | biostudies-literature
| S-EPMC4096757 | biostudies-literature
| S-EPMC1525243 | biostudies-literature
| S-EPMC2857444 | biostudies-literature
| S-EPMC4841451 | biostudies-literature