RRC ID 21540
Author Shin SY, Choi C, Lee HG, Lim Y, Lee YH.
Title Transcriptional regulation of the interleukin-11 gene by oncogenic Ras.
Journal Carcinogenesis
Abstract Interleukin-11 (IL-11), which belongs to a class of IL6-type cytokines, plays an important role in inflammation, motility and invasion in cancer. The ras mutation is frequently found in human cancer, but little is known regarding the transcriptional activation of the IL-11 gene by the Ras signal pathway in tumour cells. In this study, we investigated the role of Ras in the regulation of IL-11 using two different cell model systems: mouse NIH3T3 cells over-expressing oncogenic Ras with a tet-on system and Capan-1 human pancreatic carcinoma cells harbouring a K-ras mutation. We found that IL-11 expression was up-regulated at the transcriptional level by oncogenic Ras. Activation of the AP-1 response element, located between -153 and -30 in the 5'-regulatory region of the IL-11 gene, was necessary for oncogenic Ras-induced IL-11 promoter activation. AP-1 proteins, including Fra-1 and Fra-2, were up-regulated through the Raf/MEK and phosphatidylinositol 3-kinase (PI3K)/Akt pathways by oncogenic Ras. Knockdown of Fra-1 by siRNA in NIH3T3 or Capan-1 cells strongly attenuated oncogenic Ras-induced IL-11 expression. Additionally, inhibition of JNK, p38 and Stat3 abrogated oncogenic Ras-induced IL-11 expression. These results suggest that both the PI3K and Raf pathways are necessary for the expression of IL-11 in oncogenic Ras-mutated cells, and that JNK, p38 and Stat3 also contribute to oncogenic Ras-induced IL-11 expression.
Volume 33(12)
Pages 2467-76
Published 2012-12
DOI 10.1093/carcin/bgs297
PII bgs297
PMID 23027619
MeSH Animals Gene Expression Regulation* Genes, ras / physiology* HEK293 Cells Humans Interleukin-11 / genetics* Mice Mutation NIH 3T3 Cells Neoplasm Invasiveness Phosphatidylinositol 3-Kinases / physiology Promoter Regions, Genetic Proto-Oncogene Proteins c-fos / physiology Transcription Factor AP-1 / physiology Transcription, Genetic raf Kinases / physiology
IF 4.004
Times Cited 14
DNA material pEF-Flag-mSTATY705F (RDB02354)