title: Role of enolase-1 in response to hypoxia in breast cancer: exploring the mechanisms of action.
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.
authors: Department of Hepatobiliary Surgery, Shandong Cancer Hospital, Shandong Academy of Medical Sciences, Jinan 276000, PR China.
authors: Jie
authors: J
authors: Gao
authors: Rongrong
authors: R
authors: Zhao
authors: Yan
authors: Y
authors: Xue
authors: Zuoxing
authors: Z
authors: Niu
authors: Kai
authors: K
authors: Cui
authors: Fachang
authors: F
authors: Yu
authors: Bo
authors: B
authors: Zhang
authors: Sheng
authors: S
authors: Li
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology / Q000532:radiotherapy; D015687:Cell Hypoxia / Q000235:genetics*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D005260:Female; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D009389:Neovascularization, Pathologic / Q000235:genetics; D010751:Phosphopyruvate Hydratase / Q000235:genetics* / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D025521:Tumor Suppressor Proteins / Q000235:genetics* / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D034741:RNA, Small Interfering; D025521:Tumor Suppressor Proteins; D042461:Vascular Endothelial Growth Factor A; C095157:ENO1 protein, human; D010751:Phosphopyruvate Hydratase