p38 signaling-mediated hypoxia-inducible factor 1 alpha and vascular endothelial growth factor induction by Cr(VI) in DU145 human prostate carcinoma cells.
Gao-N; Jiang-BH; Leonard-SS; Corum-L; Zhang-Z; Roberts-JR; Antonini-J; Zheng-JZ; Flynn-DC; Castranova-V; Shi-X
J Biol Chem 2002 Nov; 277(47):45041-45048
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-1alpha but not HIF-1beta 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-1alpha 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 H(2)O(2). 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.
Cancer; Carcinogens; Carcinomas; Cell-biology; Cell-growth; Cellular-function; Chemical-kinetics; Chemical-properties; Chemical-reactions; Chromium-compounds; Humans; Tumors; Hypoxia; Prostate-cancer; Mutation; Gene-mutation; Genes; Genotoxic-effects; Biochemical-analysis; Biochemical-tests; Immunological-tests; Biochemistry
Mary Babb Randolph Cancer Center, Department of Microbiology, Immunology and Cell Biology, West Virginia University, Morgantown, West Virginia 26506-9300, USA
Research Tools and Approaches: Cancer Research Methods
Journal of Biological Chemistry