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

被引：63

作者：

Wang, Jaw-Yuan ^{[1
,2
,3
,4
,5
]}

Chen, Ben-Kuen ^{[9
]}

Wang, Yu-Shiuan ^{[1
]}

Tsai, Yao-Ting ^{[1
]}

Chen, Wei-Chiao ^{[1
]}

Chang, Wen-Chang ^{[6
,7
]}

Hou, Ming-Feng ^{[3
]}

Wu, Yang-Chang ^{[8
,10
,11
]}

Chang, Wei-Chiao ^{[1
,3
,12
]}

机构：

[1] Kaohsiung Med Univ, Dept Med Genet, Coll Med, 100 TzYou 1st Rd, Kaohsiung 807, Taiwan

[2] Kaohsiung Med Univ Hosp, Div Gastrointestinal & Gen Surg, Coll Med, Kaohsiung, Taiwan

[3] Kaohsiung Med Univ Hosp, Ctr Canc, Coll Med, Kaohsiung, Taiwan

[4] Kaohsiung Med Univ, Dept Surg, Coll Med, Kaohsiung 807, Taiwan

[5] Kaohsiung Med Univ, Grad Inst Med, Coll Med, Kaohsiung 807, Taiwan

[6] Natl Cheng Kung Univ, Coll Med, Dept Pharmacol, Tainan 70101, Taiwan

[7] Taipei Med Univ, Coll Med, Taipei, Taiwan

[8] China Med Univ, Coll Chinese Med, Grad Inst Integrated Med, Taichung, Taiwan

[9] Natl Cheng Kung Univ, Inst Bioinforrnat & Biosignal Transduct, Coll Biosci & Biotechnol, Tainan 70101, Taiwan

[10] China Med Univ Hosp, Nat Med Prod Res Ctr, Taichung, Taiwan

[11] China Med Univ Hosp, Ctr Mol Med, Taichung, Taiwan

[12] Kaohsiung Med Univ, Ctr Resources Res & Dev, Kaohsiung 807, Taiwan

来源：

CELLULAR SIGNALLING | 2012年 / 24卷 / 01期

关键词：

ORAI1/CRACM1; STIM1; Store-operated calcium channel; EGF; Cyclooxygenase-2; GROWTH-FACTOR RECEPTOR; COLORECTAL-CANCER; COLON-CANCER; CYCLOOXYGENASE-2; EXPRESSION; MUTATION STATUS; KRAS MUTATIONS; CETUXIMAB; INHIBITION; OVEREXPRESSION; RISK;

D O I：

10.1016/j.cellsig.2011.08.017

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

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 Ca2+ channel inhibitor. Transfection of siRNA against ORAI1 or STIM1, the key regulators of store-operated Ca2+ channels, showed significant inhibitory effects on EGF-mediated COX-2 expression. In conclusion, store-operated Ca2+ 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. (C) 2011 Elsevier Inc. All rights reserved.

引用

页码：162 / 169

页数：8

共 48 条

[1] EGFR, HER-2 and COX-2 levels in colorectal cancer [J].