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Article

Hypoxia regulates the expression and localization of CCAAT/enhancer binding protein α by hypoxia inducible factor‑1α in bladder transitional carcinoma cells

  • Authors:
    • Mei Xue
    • Xu Li
    • Wei Chen
  • View Affiliations / Copyright

    Affiliations: Center for Translational Medicine, The First Affiliated Hospital, School of Medicine, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China, Department of Laboratory Medicine, The First Affiliated Hospital, School of Medicine, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China
  • Pages: 2121-2127
    |
    Published online on: March 27, 2015
       https://doi.org/10.3892/mmr.2015.3563
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Abstract

Hypoxia inducible factor-1α (HIF-1α) is overexpressed in various types of solid tumor in humans, including bladder cancer. HIF-1α regulates the expression of a series of genes, which are involved in cell proliferation, differentiation, apoptosis, angiogenesis, migration and invasion and represents a potential therapeutic target for the treatment of human cancer. Despite extensive investigation of the effects of HIF‑1α in the progression and metastasis of bladder cancer, the possible regulatory mechanisms underlying the effects of HIF‑1α on bladder cancer cell proliferation and differentiation remain to be elucidated. It has been suggested that the transcription factor CCAAT/enhancer binding protein α (C/EBPα) acts as a tumor suppressor in several types of cancer cell, which are involved in regulating cell differentiation, proliferation and apoptosis. The present study confirmed that, in bladder cancer cells, the expression and localization of C/EBPα was regulated by hypoxia through an HIF‑1α‑dependent mechanism, which may be significant in bladder cancer cell proliferation and differentiation. The 5637 and T24 bladder cancer cell lines were incubated under normoxic and hypoxic conditions. The expression levels of HIF‑1α and C/EBPα were detected by reverse transcription-quantitative polymerase chain reaction, western blotting and immunofluorescence analysis. The results revealed that, under hypoxic conditions, the protein expression levels of HIF‑1α were markedly upregulated, but the mRNA levels were not altered. However, the mRNA and protein levels of C/EBPα were significantly reduced. The present study further analyzed the subcellular localization of C/EBPα, which was markedly decreased in the nuclei under hypoxic conditions. Following HIF‑1α small interference RNA silencing of HIF‑1α, downregulation of C/EBPα was prevented in the bladder cancer cells cultured under hypoxic conditions. In addition, groups of cells treated with 3‑(5'‑hydroxymethyl‑2'‑furyl)‑1‑benzylindazole, which inhibits the expression of HIF‑1α in hypoxia, contributed to the inhibited expression of HIF‑1α and enhanced expression of C/EBPα in hypoxic bladder cancer cells. These results suggested that C/EBPα was a downstream effector regulated by HIF‑1α in hypoxic bladder cancer cells and that this regulatory pathway may represent a potential therapeutic target in the treatment of bladder cancer.
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Copy and paste a formatted citation
Spandidos Publications style
Xue M, Li X and Chen W: Hypoxia regulates the expression and localization of CCAAT/enhancer binding protein α by hypoxia inducible factor‑1α in bladder transitional carcinoma cells. Mol Med Rep 12: 2121-2127, 2015.
APA
Xue, M., Li, X., & Chen, W. (2015). Hypoxia regulates the expression and localization of CCAAT/enhancer binding protein α by hypoxia inducible factor‑1α in bladder transitional carcinoma cells. Molecular Medicine Reports, 12, 2121-2127. https://doi.org/10.3892/mmr.2015.3563
MLA
Xue, M., Li, X., Chen, W."Hypoxia regulates the expression and localization of CCAAT/enhancer binding protein α by hypoxia inducible factor‑1α in bladder transitional carcinoma cells". Molecular Medicine Reports 12.2 (2015): 2121-2127.
Chicago
Xue, M., Li, X., Chen, W."Hypoxia regulates the expression and localization of CCAAT/enhancer binding protein α by hypoxia inducible factor‑1α in bladder transitional carcinoma cells". Molecular Medicine Reports 12, no. 2 (2015): 2121-2127. https://doi.org/10.3892/mmr.2015.3563
Copy and paste a formatted citation
x
Spandidos Publications style
Xue M, Li X and Chen W: Hypoxia regulates the expression and localization of CCAAT/enhancer binding protein α by hypoxia inducible factor‑1α in bladder transitional carcinoma cells. Mol Med Rep 12: 2121-2127, 2015.
APA
Xue, M., Li, X., & Chen, W. (2015). Hypoxia regulates the expression and localization of CCAAT/enhancer binding protein α by hypoxia inducible factor‑1α in bladder transitional carcinoma cells. Molecular Medicine Reports, 12, 2121-2127. https://doi.org/10.3892/mmr.2015.3563
MLA
Xue, M., Li, X., Chen, W."Hypoxia regulates the expression and localization of CCAAT/enhancer binding protein α by hypoxia inducible factor‑1α in bladder transitional carcinoma cells". Molecular Medicine Reports 12.2 (2015): 2121-2127.
Chicago
Xue, M., Li, X., Chen, W."Hypoxia regulates the expression and localization of CCAAT/enhancer binding protein α by hypoxia inducible factor‑1α in bladder transitional carcinoma cells". Molecular Medicine Reports 12, no. 2 (2015): 2121-2127. https://doi.org/10.3892/mmr.2015.3563
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