Colon Cancer Research Today is a free monthly online journal that collates and summarizes the latest research about Colon Cancer, including details on causes, treatment, symptoms.

Bombesin induces cyclooxygenase-2 expression through the activation of the nuclear factor of activated T cells and enhances cell migration in Caco-2 colon carcinoma cells.

Corral RS, Iñiguez MA, Duque J, López-Pérez R, Fresno M

Centro de Biología Molecular 'Severo Ochoa', Universidad Autónoma de Madrid-CSIC, Madrid, Spain.

Cyclooxygenase-2 (Cox-2), the gastrin-release peptide (GRP) and its cognate receptor (GRP-R) are overexpressed in a significant percentage of colorectal carcinomas and are associated with cell growth, invasiveness and tumor progression. However, a molecular link between all of them in adenocarcinomas has not been established. Here, we show that bombesin (BBS), a GRP homolog, stimulates the expression of Cox-2 mRNA and protein in human colon adenocarcinoma Caco-2 cells, resulting in enhanced release of prostaglandin E(2). These effects were markedly inhibited by the specific BBS antagonist RC-3940-II. BBS promotes the activation of the nuclear factor of activated T cells (NFAT) through a Ca(2+)/calcineurin (Cn)-linked pathway. Upon BBS stimulation, the NFATc1 isoform translocates into the nucleus with a concomitant increase in NFATc1 binding to two specific recognition sites in the promoter region of the Cox-2 gene. Furthermore, inhibition of Cn activity by the immunosuppressive drug cyclosporin A impaired NFAT activation and diminished Cox-2 expression in BBS-stimulated cells. Interestingly, BBS pretreatment strongly enhances the invasive capacity of carcinoma cells, effect which was inhibited by a Cox-2-specific inhibitor. These findings provide the first evidence for the involvement of the Ca(2+)/Cn/NFAT pathway in BBS-mediated induction of genes involved in colon carcinoma invasiveness such as Cox-2.

Published 15 February 2007 in Oncogene, 26(7): 958-69.
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