c-Myb increases resistance of colon carcinoma cells to cisplatin by activation of MAPKp38δ and JNK/c-Jun signaling pathways
| Autoři | |
|---|---|
| Rok publikování | 2013 |
| Druh | Konferenční abstrakty |
| Fakulta / Pracoviště MU | |
| Citace | |
| Popis | c-Myb is a transcription factor playing essential role in control of proliferation, differentiation and apoptosis of epithelial cells. Its malfunction has been associated with various tumors. Patients with colorectal carcinomas (CRC) exhibiting upregulated c-Myb expression have poor prognosis. The aim of this study was to clarify the role of c-Myb in control of the cell death/survival of colorectal carcinoma cells treated with cytotoxic agents. Our results show that the c-Myb protein reduced sensitivity of colorectal carcinoma cells to cisplatin and doxorubicin. We identified the downstream effectors mediating the effects c-Myb on cell viability - MAPKp38 and c-Jun kinases. Selective inhibitors of these kinases were used to prove the potential link between c-Myb upregulation and improved survival of colorectal cells exposed to cisplatin. Using a panel of p38 inhibitors we identified MAPKp38delta isoform (MAPK13) as a key molecule in mediating this effect. In this work, we present the possibility of a novel c-Myb-p38delta/JNK signal axis mediating increased resistance of colorectal cells to cytotoxic agents. |
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