p38 Signaling-Mediated Hypoxia-Inducible Factor 1 Alpha and Vascular Endothelial Growth Factor Induction by Cr(VI) in DU145 Human Prostate Carcinoma Cells
Public Domain
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2002/11/22
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Details
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Personal Author:Antonini J ; Castranova, Vincent ; Corum L ; Flynn DC ; Gao N ; Jiang BH ; Leonard, Stephen S. ; Roberts, Jennifer R. ; Shi X ; Zhang Z ; Zheng JZ
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Description: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. [Description provided by NIOSH]
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ISSN:0021-9258
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Volume:277
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Issue:47
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NIOSHTIC Number:nn:20022382
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Citation:J Biol Chem 2002 Nov; 277(47):45041-45048
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Contact Point Address:Mary Babb Randolph Cancer Center, Department of Microbiology, Immunology and Cell Biology, West Virginia University, Morgantown, West Virginia 26506-9300, USA
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Email:bhjiang@hsc.wvu.edu
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Federal Fiscal Year:2003
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Peer Reviewed:True
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Source Full Name:Journal of Biological Chemistry
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Main Document Checksum:urn:sha-512:149c646d817c292811311abb88f1ebc8b0b1a77303964272779095cc4c306d6b88f9658a3babccbfa2b3578151942675424291e8154fc52ee9a68d7b68d683b0
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