The c-Myb-induced resistance of colon cancer cells to cisplatin is mediated by the p38 MAP kinase

Authors

PEKARČÍKOVÁ Lucie KNOPFOVÁ Lucia BENEŠ Petr HERMANOVÁ Markéta TICHÝ Michal ŠMARDA Jan

Year of publication 2013
Type Conference abstract
Citation
Description Background: The c-Myb transcription factor is essential for maintenance of stem-progenitor cells in colon epithelia and its expression is deregulated in premalignant adenomatous polyps and colorectal carcinomas. Patients with colorectal carcinoma exhibiting upregulated c- Myb expression have poor prognosis. This can result from low sensitivity of cancer cells to cytotoxic agents. Methods: In our study, increased resistance of colon carcinoma CT26 and HCT116 cells overproducing exogenous c-Myb to cytotoxic agents was observed. These cells lost sensitivity to cisplatin and doxorubicin upon upregulation of c-Myb. The effect of c-Myb can be mediated by the mitogen-activated protein kinase (MAPK) signaling since phosphorylation of the MAPKs p38 and JNK was enhanced in cells exhibiting high expression of exogenous c-Myb. Results: To determine functional contribution of these kinases to resistance of the c-Myb-overexpressing cells to cisplatin, we used BIRB796 to inhibit activity of p38 and SP600125 to inhibit JNK. We found that the c-Myb-induced resistance of CT26 cells to cisplatin can be reversed by BIRB796. Conclusions: This result documents that it is the p38 kinase that mediates the effects of c-Myb on sensitivity of colon cancer CT26 cells to cisplatin (This study was supported by grant NT13441/2012 of the Internal Grant Agency of the Ministry of Health, Czech Republic).
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