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Articles by K Kragballe
Total Records ( 2 ) for K Kragballe
  C Johansen , C Vestergaard , K Kragballe , G Kollias , M Gaestel and L. Iversen
 

The association between inflammation and tumorigenesis is well recognized. Mitogen-activated protein kinase-activated protein kinase-2 (MK2) is known to play a pivotal role in inflammatory processes. Here, we studied the effect of MK2-deficiency and tumor necrosis factor (TNF)--deficiency on skin tumor development in mice using the two-stage chemical carcinogenesis model. We found that MK2–/– mice developed significantly fewer skin tumors compared with both TNF-–/– and wild-type mice when induced by initiation with 7,12-dimethylbenz[a]anthracene (DMBA) and by promotion with 12-O-tetradecanoylphorbol-13-acetate (TPA). The TPA-induced inflammatory response was reduced in both, TNF-–/– mice and MK2–/– mice, but most pronounced in TNF-–/– mice, indicating that a reduced inflammatory response was not the only explanation for the inhibited tumorigenesis seen in MK2–/– mice. Interestingly, increased numbers of apoptotic cells were detected in the epidermis of MK2–/– mice compared with TNF-–/– and wild-type mice, suggesting an additional role of MK2 in the regulation of apoptosis. This was further supported by: (i) increased levels of the tumor suppressor protein p53 in MK2–/– mice after DMBA/TPA treatment compared with controls, (ii) reduced phosphorylation (activation) of the negative p53 regulator, murine double minute 2 in MK2/ mouse keratinocytes in vitro and (iii) a significant decrease in the DMBA/TPA induced apoptosis in cultured MK2–/– keratinocytes transfected with p53 small interfering RNA. Taken together, these findings demonstrate a dual role of MK2 in the early stages of tumor promotion through regulation of both the inflammatory response and apoptosis of DNA-damaged cells. These results also identify MK2 as a putative target for future skin carcinoma therapy.

 
 
 
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