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

55 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

Fingerprint

Calcium Signaling
Cyclooxygenase 2
Epidermal Growth Factor
Transcriptional Activation
Epidermal Growth Factor Receptor
Neoplasms
Colorectal Neoplasms
NFATC Transcription Factors
TCF Transcription Factors
Cyclic AMP
Small Interfering RNA
Transfection
Interleukin-6
Carcinogenesis
Transcription Factors
Binding Sites
Neoplasm Metastasis
Inflammation
Gene Expression
Genes

Keywords

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

ASJC Scopus subject areas

  • Cell Biology

Cite this

Involvement of store-operated calcium signaling in EGF-mediated COX-2 gene activation in cancer cells. / Wang, Jaw Yuan; Chen, Ben Kuen; Wang, Yu Shiuan; Tsai, Yao Ting; Chen, Wei Chiao; Chang, Wen Chang; Hou, Ming Feng; Wu, Yang Chang; Chang, Wei Chiao.

In: Cellular Signalling, Vol. 24, No. 1, 01.2012, p. 162-169.

Research output: Contribution to journalArticle

Wang, Jaw Yuan ; Chen, Ben Kuen ; Wang, Yu Shiuan ; Tsai, Yao Ting ; Chen, Wei Chiao ; Chang, Wen Chang ; Hou, Ming Feng ; Wu, Yang Chang ; Chang, Wei Chiao. / Involvement of store-operated calcium signaling in EGF-mediated COX-2 gene activation in cancer cells. In: Cellular Signalling. 2012 ; Vol. 24, No. 1. pp. 162-169.
@article{f80ae3e526fe4b99bc029f9a5f7751d6,
title = "Involvement of store-operated calcium signaling in EGF-mediated COX-2 gene activation in cancer cells",
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.",
keywords = "Cyclooxygenase-2, EGF, ORAI1/CRACM1, STIM1, Store-operated calcium channel",
author = "Wang, {Jaw Yuan} and Chen, {Ben Kuen} and Wang, {Yu Shiuan} and Tsai, {Yao Ting} and Chen, {Wei Chiao} and Chang, {Wen Chang} and Hou, {Ming Feng} and Wu, {Yang Chang} and Chang, {Wei Chiao}",
year = "2012",
month = "1",
doi = "10.1016/j.cellsig.2011.08.017",
language = "English",
volume = "24",
pages = "162--169",
journal = "Cellular Signalling",
issn = "0898-6568",
publisher = "Elsevier Inc.",
number = "1",

}

TY - JOUR

T1 - Involvement of store-operated calcium signaling in EGF-mediated COX-2 gene activation in cancer cells

AU - Wang, Jaw Yuan

AU - Chen, Ben Kuen

AU - Wang, Yu Shiuan

AU - Tsai, Yao Ting

AU - Chen, Wei Chiao

AU - Chang, Wen Chang

AU - Hou, Ming Feng

AU - Wu, Yang Chang

AU - Chang, Wei Chiao

PY - 2012/1

Y1 - 2012/1

N2 - 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.

AB - 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.

KW - Cyclooxygenase-2

KW - EGF

KW - ORAI1/CRACM1

KW - STIM1

KW - Store-operated calcium channel

UR - http://www.scopus.com/inward/record.url?scp=80755132231&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=80755132231&partnerID=8YFLogxK

U2 - 10.1016/j.cellsig.2011.08.017

DO - 10.1016/j.cellsig.2011.08.017

M3 - Article

C2 - 21924350

AN - SCOPUS:80755132231

VL - 24

SP - 162

EP - 169

JO - Cellular Signalling

JF - Cellular Signalling

SN - 0898-6568

IS - 1

ER -