Involvement of store-operated calcium signaling in EGF-mediated COX-2 gene activation in cancer cells

Jaw Yuan Wang, Ben Kuen Chen, Yu Shiuan Wang, Yao Ting Tsai, Wei Chiao Chen, Wen Chang Chang, Ming Feng Hou, Yang Chang Wu, Wei Chiao Chang

Research output: Contribution to journalArticle

57 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)162-169
Number of pages8
JournalCellular Signalling
Volume24
Issue number1
DOIs
Publication statusPublished - Jan 2012
Externally publishedYes

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Keywords

  • Cyclooxygenase-2
  • EGF
  • ORAI1/CRACM1
  • STIM1
  • Store-operated calcium channel

ASJC Scopus subject areas

  • Cell Biology

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