Prostaglandin E2 induces the expression of IL-1alpha in colon cancer cells
Shao, J.; Sheng, H.
Journal of Immunology 178(7): 4097-4103
2007
ISSN/ISBN: 0022-1767 PMID: 17371964 Document Number: 610511
PGE(2) has been shown to exert pro-oneogenic effects in colorectal neoplasia through producing autocrine or paracrine growth factors. In the present study, we demonstrate that PGE(2) induced the expression of IL-1 alpha in colon cancer cells, which plays critical roles in tumor metastasis and neoangiogenesis in a variety of cancers. PGE(2) increased the levels of both IL-1 alpha mRNA and protein, suggesting a positive feedback loop between the IL-1 pathway and PGE2 signaling. Mechanistically, PGE(2) induced the expression of IL-1 alpha at both transcriptional and posttranscriptional levels. PGE, stimulated the transcriptional activity of the IL-1 alpha promoter and significantly stabilized IL-1 alpha mRNA. Moreover, we show that IL-1 alpha enhanced colorectal neoplasia, stimulating cell migration and neoangiogenesis. Knockdown of the expression of IL-1 alpha by small -interfering RNA resulted in a reduction of vascular endothelial growth factor secretion in colon cancer cells and an inhibition of tube formation by HUVECs. Thus, our results suggest that PGE, induces the expression of proinfiammatory cytokine IL-1 alpha, which may potentially enhance the proneoplastic actions of the cyclooxygenase-2/PGE2 signaling pathway.