Dataset Information

PI3K and ERK-induced Rac1 activation mediates hypoxia-induced HIF-1? expression in MCF-7 breast cancer cells.

ABSTRACT:

Background

Hypoxia-inducible factor 1 (HIF-1?) expression induced by hypoxia plays a critical role in promoting tumor angiogenesis and metastasis. However, the molecular mechanisms underlying the induction of HIF-1? in tumor cells remain unknown.

Methodology/principal findings

In this study, we reported that hypoxia could induce HIF-1? and VEGF expression accompanied by Rac1 activation in MCF-7 breast cancer cells. Blockade of Rac1 activation with ectopic expression of an inactive mutant form of Rac1 (T17N) or Rac1 siRNA downregulated hypoxia-induced HIF-1? and VEGF expression. Furthermore, Hypoxia increased PI3K and ERK signaling activity. Both PI3K inhibitor LY294002 and ERK inhibitor U0126 suppressed hypoxia-induced Rac1 activation as well as HIF-1? expression. Moreover, hypoxia treatment resulted in a remarkable production of reactive oxygen species (ROS). N-acetyl-L-cysteine, a scavenger of ROS, inhibited hypoxia-induced ROS generation, PI3K, ERK and Rac1 activation as well as HIF-1? expression.

Conclusions/significance

Taken together, our study demonstrated that hypoxia-induced HIF-1? expression involves a cascade of signaling events including ROS generation, activation of PI3K and ERK signaling, and subsequent activation of Rac1.

SUBMITTER: Du J

PROVIDER: S-EPMC3181265 | biostudies-literature | 2011

REPOSITORIES: biostudies-literature

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Publications

PI3K and ERK-induced Rac1 activation mediates hypoxia-induced HIF-1α expression in MCF-7 breast cancer cells.

Du Jun J Xu Rui R Hu Zhenzhen Z Tian Yinhui Y Zhu Yichao Y Gu Luo L Zhou Lei L

PloS one 20110927 9

<h4>Background</h4>Hypoxia-inducible factor 1 (HIF-1α) expression induced by hypoxia plays a critical role in promoting tumor angiogenesis and metastasis. However, the molecular mechanisms underlying the induction of HIF-1α in tumor cells remain unknown.<h4>Methodology/principal findings</h4>In this study, we reported that hypoxia could induce HIF-1α and VEGF expression accompanied by Rac1 activation in MCF-7 breast cancer cells. Blockade of Rac1 activation with ectopic expression of an inactive ...[more]

PMID: 21980400

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