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12-Lipoxygenase and the regulation of hypoxia-inducible factor in prostate cancer cells.

Abstract：

:12-Lipoxygenase, an arachidonic acid metabolizing enzyme of the lipoxygenase pathway, has been implicated as a major factor in promoting prostate cancer progression and metastasis. The ability of 12-LOX to aggravate the disease was linked to its proangiogenic role. Recent studies clearly demonstrated that 12-LOX enhances the expression and secretion of the angiogenic factor, vascular endothelial growth factor (VEGF) thus providing a direct link between this enzyme and its angiogenic properties. In the present study we have investigated the relationship between 12-LOX and hypoxia inducible factor-1alpha (HIF-1alpha), a transcription factor involved in the regulation of VEGF expression under hypoxic conditions in solid tumors. Our findings have revealed that HIF-1 is one of the target transcription factors regulated by 12-LOX and 12(S)-HETE, in hypoxic tumor cells of the prostate. Regulation of HIF-1alpha by 12-LOX adds to the complexity of pathways mediated by this enzyme in promoting prostate cancer angiogenesis and metastasis. We have evidence that 12-LOX increases the protein level, mRNA, and functional activity of HIF-1alpha under hypoxic conditions, one of the mechanisms by which it upregulates VEGF secretion and activity.

journal_name

Exp Cell Res

journal_title

Experimental cell research

authors

Krishnamoorthy S,Jin R,Cai Y,Maddipati KR,Nie D,Pagès G,Tucker SC,Honn KV

doi

10.1016/j.yexcr.2010.03.005

subject

Has Abstract

pub_date

2010-06-10 00:00:00

pages

1706-15

issue

10

eissn

0014-4827

issn

1090-2422

pii

S0014-4827(10)00112-6

journal_volume

316

pub_type

杂志文章

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