Ras-induced interleukin-8 expression plays a critical role in tumor growth and angiogenesis.
The role of Ras oncogenes in promoting cellular transformation is well established. However, the contribution of Ras signaling to interactions between tumor cells and their host environment remains poorly characterized. Here, we demonstrate that the inflammatory mediator interleukin-8 (CXCL-8/IL-8) is a transcriptional target of Ras signaling. Using a tumor xenograft model, we show that Ras-dependent CXCL-8 secretion is required for the initiation of tumor-associated inflammation and neovascularization. Collectively, our data identify a novel mechanism by which the Ras oncogene can elicit a stromal response that fosters cancer progression.
Sparmann
Anke
A
Graduate Program in Molecular Genetics and Microbiology, State University of New York at Stony Brook, Stony Brook, New York 11794, USA.
Bar-Sagi
Dafna
D
D000818:Animals; D002465:Cell Movement; D042783:Endothelial Cells / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic; D011905:Genes, ras; D006367:HeLa Cells; D006801:Humans; D007249:Inflammation / Q000235:genetics; D016209:Interleukin-8 / Q000096:biosynthesis* / Q000276:immunology / Q000494:pharmacology; D051379:Mice; D008819:Mice, Nude; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism; D009369:Neoplasms / Q000235:genetics* / Q000473:pathology*; D009389:Neovascularization, Pathologic / Q000235:genetics*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D015398:Signal Transduction; D014162:Transfection
D016209:Interleukin-8; D019869:Phosphatidylinositol 3-Kinases; D020929:Mitogen-Activated Protein Kinase Kinases