Get 20M+ Full-Text Papers For Less Than $1.50/day. Start a 14-Day Trial for You or Your Team.

Learn More →

Role of enolase-1 in response to hypoxia in breast cancer: Exploring the mechanisms of action

Role of enolase-1 in response to hypoxia in breast cancer: Exploring the mechanisms of action In the present study, we investigated the effect of reduced enolase-1 expression in human umbilical vein endothelial cells (HUVECs)/MDA-MB-231 cells on the response to hypoxia and the possible mechanisms involved. Breast cancer cells transfected with enolase-1 siRNA were injected into mice to establish a tumor-bearing mouse model, and the correlation between enolase-1 expression and breast cancer angiogenesis, as well as its effect on the efficacy of radiation therapy were assessed. HUVECs were cultured in vitro, and transfected with enolase-1 siRNA. Following stable passage, 1.0% O2 was used to induce hypoxia. The growth, proliferation, division and angiogenesis of HUVECs were observed using MTT assay, flow cytometry (FCM) and time-lapse video microscopy. The key regulatory molecules were detected using western blot analysis, two-dimensional (2-D) electrophoresis and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS). The breast cancer cell line, MDA-MB-231, was cultured in vitro, and transfected with enolase-1 siRNA. The cells were injected into nude mice, and radiation therapy was administered. Tumor growth, angiogenesis in tumor tissues and apoptosis were observed, and the expression of the endogenous hypoxia marker, hypoxia inducible factor-1α (HIF-1α), was detected using immunohistochemistry after the mice were sacrificed. A significant reduction in the hypoxia-induced apoptosis of HUVECs was observed in the control group compared with the endothelial cells transfected with enolase-1 siRNA. After the enolase-1 transfected breast cancer cells were injected into nude mice, tumor growth significantly declined, and the tumor volume and weight were reduced. Following treatment with radiation therapy, tumor size significantly decreased in both groups, and the highest reduction was observed in the transfected group. The reduction in enolase-1 expression significantly decreases the response to hypoxia and enhances the sensitivity of the cells to radiation therapy; therefore, enolase-1 may be a drug target for the treatment of breast cancer. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Oncology Reports Spandidos Publications

Role of enolase-1 in response to hypoxia in breast cancer: Exploring the mechanisms of action

Download PDF
11 pages

Loading next page...
 
/lp/spandidos-publications/role-of-enolase-1-in-response-to-hypoxia-in-breast-cancer-exploring-8Ss0vcEgrU

References

References for this paper are not available at this time. We will be adding them shortly, thank you for your patience.

Publisher
Spandidos Publications
Copyright
Copyright © Spandidos Publications
ISSN
1021-335X
eISSN
1791-2431
DOI
10.3892/or.2013.2269
pmid
23381546
Publisher site
See Article on Publisher Site

Abstract

In the present study, we investigated the effect of reduced enolase-1 expression in human umbilical vein endothelial cells (HUVECs)/MDA-MB-231 cells on the response to hypoxia and the possible mechanisms involved. Breast cancer cells transfected with enolase-1 siRNA were injected into mice to establish a tumor-bearing mouse model, and the correlation between enolase-1 expression and breast cancer angiogenesis, as well as its effect on the efficacy of radiation therapy were assessed. HUVECs were cultured in vitro, and transfected with enolase-1 siRNA. Following stable passage, 1.0% O2 was used to induce hypoxia. The growth, proliferation, division and angiogenesis of HUVECs were observed using MTT assay, flow cytometry (FCM) and time-lapse video microscopy. The key regulatory molecules were detected using western blot analysis, two-dimensional (2-D) electrophoresis and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS). The breast cancer cell line, MDA-MB-231, was cultured in vitro, and transfected with enolase-1 siRNA. The cells were injected into nude mice, and radiation therapy was administered. Tumor growth, angiogenesis in tumor tissues and apoptosis were observed, and the expression of the endogenous hypoxia marker, hypoxia inducible factor-1α (HIF-1α), was detected using immunohistochemistry after the mice were sacrificed. A significant reduction in the hypoxia-induced apoptosis of HUVECs was observed in the control group compared with the endothelial cells transfected with enolase-1 siRNA. After the enolase-1 transfected breast cancer cells were injected into nude mice, tumor growth significantly declined, and the tumor volume and weight were reduced. Following treatment with radiation therapy, tumor size significantly decreased in both groups, and the highest reduction was observed in the transfected group. The reduction in enolase-1 expression significantly decreases the response to hypoxia and enhances the sensitivity of the cells to radiation therapy; therefore, enolase-1 may be a drug target for the treatment of breast cancer.

Journal

Oncology Reports – Spandidos Publications

Published: Apr 1, 2013

References

  • Hypoxia-inducible factors: central regulators of the tumor phenotype
    Gordan
  • Bcl-x(L)-mediated changes in metabolic pathways of breast cancer cells: from survival in the blood stream to organ-specific metastasis
    España
  • Proteomic study reveals that proteins involved in metabolic and detoxification pathways are highly expressed in HER-2/neu-positive breast cancer
    Zhang
  • Proteomic analysis of paclitaxel-induced apoptosis in MCF-7 human breast carcinoma cells
    Wu
  • Proteomic analysis of isolated membrane fractions from superinvasive cancer cells
    Dowling
  • Proteomic analysis of carbonylated proteins in two-dimensional gel electrophoresis using avidin-fluorescein affinity staining
    Yoo
  • In vitro reoxygenation following hypoxia increases MMP-2 and TIMP-2 secretion by human umbilical vein endothelial cells
    Cavdar
  • Cytokines induce HIF-1 DNA binding and the expression of HIF-1-dependent genes in cultured rat enterocytes
    Scharte
  • High-throughput proteomic analysis of human infiltrating ductal carcinoma of the breast
    Somiari
  • Vitexin, an HIF-1alpha inhibitor, has anti-metastatic potential in PC12 cells
    Choi
  • Antiapoptotic action of hypoxia-inducible factor-1α in human endothelial cells
    Yu
  • Identification of hypoxia-responsive messengers expressed in human microvascular endothelial cells using differential display RT-PCR
    Roland
  • A proteomic study on cell cycle progression of endothelium exposed to tumor conditioned medium and the possible role of cyclin D1/E
    Li
  • The mitogenic and anti-apoptotic activity of tumor conditioned medium on endothelium
    Li
  • Culture of human endothelial cells derived from umbilical veins. Identification by morphologic and immunologic criteria
    Jaffe
  • Identification of tumour-induced changes in endothelial cell surface protein expression: an in vitro model
    Hewett
  • V-SRC induces expression of hypoxia-inducible factor 1 (HIF-1) and transcription of genes encoding vascular endothelial growth factor and enolase 1: involvement of HIF-1 in tumor progression
    Jiang
  • Multifaceted roles of glycolytic enzymes
    Kim
  • Reduced levels of DEAD-box proteins DBP-RB and p72 in fetal Down syndrome brains
    Kircher
  • The Smad transcriptional corepressor TGIF recruits mSin3
    Wotton
  • TGIF2 interacts with histone deacetylase 1 and represses transcription
    Melhuish
  • Prohibitins, stomatins, and plant disease response genes compose a protein superfamily that controls cell proliferation, ion channel regulation, and death
    Nadimpalli
  • Identification of protein disulfide isomerase as an endothelial hypoxic stress protein
    Graven
  • Pyruvate kinase: activation by and catalytic role of the monovalent and divalent cations
    Nowak
  • Plasma phospholipid transfer protein prevents vascular endothelium dysfunction by delivering α-tocopherol to endothelial cells
    Desrumaux
  • Transduction of folate receptor cDNA into cervical carcinoma cells using recombinant adeno-associated virions delays cell proliferation in vitro and in vivo
    Sun
  • Constructing disease-specific gene networks using pair-wise relevance metric: application to colon cancer identifies interleukin 8, desmin and enolase 1 as the central elements
    Jiang
  • Protein alterations in infiltrating ductal carcinomas of the breast as detected by nonequilibrium pH gradient electrophoresis and mass spectrometry
    Kabbage
  • Towards a lung adenocarcinoma proteome map: Studies with SP-C/c-raf transgenic mice
    Rütters
  • The involvement of hypoxia-inducible factor-1alpha in the susceptibility to gamma-rays and chemotherapeutic drugs of oral squamous cell carcinoma cells
    Sasabe
  • Tumor hypoxia: its impact on cancer therapy
    Moulder