TY - JOUR
T1 - Arsenite induces p70S6K1 activation and HIF-1α expression in prostate cancer cells
AU - Skinner, Heath D.
AU - Zhong, Xiao Song
AU - Gao, Ning
AU - Shi, Xianglin
AU - Jiang, Bing Hua
PY - 2004/1
Y1 - 2004/1
N2 - 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 (HIF1) is a basic helix-loop-helix transcription factor composed of two subunits, HIF-1α and HIF-1β. 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 levelsof p70S6K1 phosphorylation and p70S6K1 activity in a PI3K and mTOR sensitive manner. We have also shown that arsenite specifically induces HIF-1α, but not HIF-1β, protein levels in prostate cancer cells in a mTOR-dependent manner.
AB - 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 (HIF1) is a basic helix-loop-helix transcription factor composed of two subunits, HIF-1α and HIF-1β. 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 levelsof p70S6K1 phosphorylation and p70S6K1 activity in a PI3K and mTOR sensitive manner. We have also shown that arsenite specifically induces HIF-1α, but not HIF-1β, protein levels in prostate cancer cells in a mTOR-dependent manner.
KW - Arsenite
KW - HIF-1
KW - PI3K
KW - mTOR
KW - p70S6K1
UR - http://www.scopus.com/inward/record.url?scp=0742271942&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0742271942&partnerID=8YFLogxK
U2 - 10.1023/B:MCBI.0000007257.67733.3b
DO - 10.1023/B:MCBI.0000007257.67733.3b
M3 - Review article
C2 - 14971642
AN - SCOPUS:0742271942
SN - 0300-8177
VL - 255
SP - 19
EP - 23
JO - Molecular and Cellular Biochemistry
JF - Molecular and Cellular Biochemistry
IS - 1-2
ER -