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Hypoxia induces RANK and RANKL expression by activating HIF-1α in breast cancer cells.

Abstract：

:Receptor activator of NF-κB (RANK) and RANK ligand (RANKL) are known to play an important role in the development and progression of breast cancer. However, the mechanisms by which stimuli regulate the expression of RANK and RANKL in breast cancer cells are largely unknown. In this study, we show that hypoxia, a common feature of malignant tumors, can enhance the expression of RANK and RANKL mRNA and protein in MDA-MB-231 and MCF-7 breast cancer cells. In addition, we found that hypoxia induced hypoxia-inducible factor-1 alpha (HIF-1α) and phosphorylation of Akt, resulting in upregulation of RANK and RANKL expression; HIF-1α-targeted siRNA and PI3K-Akt inhibitor abrogated this upregulation in MDA-MB-231 cells. Furthermore, we also observed that hypoxia accelerated RANKL-mediated cell migration, which was inhibited following HIF-1α knockdown and PI3K-Akt inhibition. Thus, we provide evidence that hypoxia upregulates RANK and RANKL expression and increases RANKL-induced cell migration via the PI3K/Akt-HIF-1α pathway.

journal_name

Biochem Biophys Res Commun

journal_title

Biochemical and biophysical research communications

authors

Tang ZN,Zhang F,Tang P,Qi XW,Jiang J

doi

10.1016/j.bbrc.2011.04.035

subject

Has Abstract

pub_date

2011-05-13 00:00:00

pages

411-6

issue

3

eissn

0006-291X

issn

1090-2104

pii

S0006-291X(11)00609-7

journal_volume

408

pub_type

杂志文章

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