p38 signaling-mediated hypoxia-inducible factor 1α and vascular endothelial growth factor induction by Cr(VI) in DU145 human prostate carcinoma cells

Ning Gao, Bing Hua Jiang, Stephen S. Leonard, Linda Corum, Zhuo Zhang, Jenny R. Roberts, Jim Antonini, Jenny Z. Zheng, Daniel C. Flynn, Vince Castranova, Xianglin Shi

Research output: Contribution to journalArticlepeer-review

120 Scopus citations

Abstract

Chromium(VI) (Cr(VI)) is widely used in industry and is a potent inducer of tumors in animals. The present study demonstrates that Cr(VI) induces hypoxia-inducible factor 1 (HIF-1) activity through the specific expression of HIF-1α but not HIF-1β subunit and increases the level of vascular endothelial growth factor (VEGF) expression in DU145 human prostate carcinoma cells. To dissect the signaling pathways involved in Cr(VI)-induced HIF-1 expression, we found that p38 mitogen-activated protein kinase signaling was required for HIF-1α expression induced by Cr(VI). Neither phosphatidylinositol 3-kinase nor extracellular signal-regulated kinase activity was required for Cr(VI)-induced HIF-1 expression. Cr(VI) induced expression of HIF-1 and VEGF through the production of reactive oxygen species in DU145 cells. The major species of reactive oxygen species responsible for the induction of HIF-1 and VEGF expression is H2O2. These results suggest that the expression of HIF-1 and VEGF induced by Cr(VI) may be an important signaling pathway in the Cr(VI)-induced carcinogenesis.

Original languageEnglish
Pages (from-to)45041-45048
Number of pages8
JournalJournal of Biological Chemistry
Volume277
Issue number47
DOIs
StatePublished - Nov 22 2002

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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