Prostaglandin E2 induces the expression of IL-1alpha in colon cancer cells.
PGE(2) has been shown to exert pro-oncogenic 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-1alpha 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-1alpha mRNA and protein, suggesting a positive feedback loop between the IL-1 pathway and PGE(2) signaling. Mechanistically, PGE(2) induced the expression of IL-1alpha at both transcriptional and posttranscriptional levels. PGE(2) stimulated the transcriptional activity of the IL-1alpha promoter and significantly stabilized IL-1alpha mRNA. Moreover, we show that IL-1alpha enhanced colorectal neoplasia, stimulating cell migration and neoangiogenesis. Knockdown of the expression of IL-1alpha 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(2) induces the expression of proinflammatory cytokine IL-1alpha, which may potentially enhance the proneoplastic actions of the cyclooxygenase-2/PGE(2) signaling pathway.
Shao
Jinyi
J
Department of Surgery and Cancer Center, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
Sheng
Hongmiao
H
D020413:3' Untranslated Regions / Q000378:metabolism; D002465:Cell Movement; D003110:Colonic Neoplasms / Q000098:blood supply* / Q000235:genetics / Q000276:immunology*; D000242:Cyclic AMP / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D015232:Dinoprostone / Q000494:pharmacology*; D006801:Humans; D053582:Interleukin-1alpha / Q000235:genetics / Q000378:metabolism*; D009389:Neovascularization, Pathologic / Q000235:genetics / Q000276:immunology*; D011458:Prostaglandins E / Q000378:metabolism; D020871:RNA Stability / Q000187:drug effects; D012333:RNA, Messenger / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects; D014407:Tumor Cells, Cultured
D020413:3' Untranslated Regions; D053582:Interleukin-1alpha; D011458:Prostaglandins E; D012333:RNA, Messenger; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D015232:Dinoprostone