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Arsenite induces p70S6K1 activation and HIF-1alpha expression in prostate cancer cells.

Authors
Skinner-HD; Zhong-XS; Gao-N; Shi-X; Jiang-BH
Source
Mol Cell Biochem 2004 Jan; 255(1-2):19-23
NIOSHTIC No.
20025984
Abstract
Arsenite is ubiquitous in the environment, particularly in the form of contaminated water. Although this metal is a known human carcinogen, its exact mechanism of action remains unclear. P70S6K1 phosphorylates the ribosomal 40S protein leading to increased protein translation, and is an important regulator of cell growth and proliferation. Hypoxia inducible factor-1 (HIF-1) is a basic helix-loop-helix transcription factor composed of two subunits, HIF-1alpha and HIF-1beta. HIF-1 activates the transcription of a number of genes that mediate angiogenesis and tumor formation. In this study we demonstrated that arsenite treatment increased levels of p70S6K1 phosphorylation and p70S6K1 activity in a PI3K and mTOR sensitive manner. We have also shown that arsenite specifically induces HIF-1alpha, but not HIF-1beta, protein levels in prostate cancer cells in a mTOR-dependent manner.
Keywords
Arsenites; Cancer; Prostate-cancer; Metals; Carcinogens; Cell-growth; Tumors; Carcinogenesis; Carcinogenicity; Tumorigenesis; Tumorigens; Arsenic-compounds
CODEN
MCBIB8
CAS No.
15502-74-6
Publication Date
20040101
Document Type
Journal Article
Email Address
bhjiang@hsc.wvu.edu
Fiscal Year
2004
NTIS Accession No.
NTIS Price
Issue of Publication
1-2
ISSN
0300-8177
NIOSH Division
HELD
Source Name
Molecular and Cellular Biochemistry
State
WV
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