摘要
Growing evidence shows that chronic inflammation drives the progression of colorectal cancer (CRC). Cyclooxygenase-2 (COX-2) is one of the most important inflammatory genes involved in solid tumor metastasis. Epidermal growth factor receptor (EGFR) also plays a key role in cancer cell development. We compared the expression levels of EGFR and COX-2 between tumor and normal tissues from 20 CRC patients and studied the molecular mechanism of EGFR-mediated COX-2 gene expression in cancer cells. Our results indicated that COX-2 expression was markedly increased after EGF stimulation. COX-2 promoter analysis indicated the involvement of cyclic AMP-responsive element (CRE) and nuclear factor of activated T cells/nuclear factor interleukin-6 (NFAT/NF-IL6)-binding sites in EGF-mediated signaling pathways. Furthermore, EGF-mediated COX-2 activation was prevented by 2-aminoethoxydiphenyl borate (2-APB), a store-operated Ca 2+ channel inhibitor. Transfection of siRNA against ORAI1 or STIM1, the key regulators of store-operated Ca 2+ channels, showed significant inhibitory effects on EGF-mediated COX-2 expression. In conclusion, store-operated Ca 2+ entry is involved in the activation of transcription factors (CREB/NFAT) that are responsible for delivering EGF-mediated signals to evoke inflammatory cascades and is eventually related to CRC tumorigenesis.
原文 | 英語 |
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頁(從 - 到) | 162-169 |
頁數 | 8 |
期刊 | Cellular Signalling |
卷 | 24 |
發行號 | 1 |
DOIs | |
出版狀態 | 已發佈 - 1月 2012 |
對外發佈 | 是 |
ASJC Scopus subject areas
- 細胞生物學