Expression and significance of hypoxia-inducible factor-1α and survivin in laryngeal carcinoma tissue and cells

Otolaryngol Head Neck Surg. 2013 Jan;148(1):75-81. doi: 10.1177/0194599812464759. Epub 2012 Oct 19.

Abstract

Objective: The aim was to evaluate hypoxia-inducible factor-1α (HIF-1α) and survivin expression in laryngeal squamous cell carcinoma (LSCC) tissues and cell lines and to investigate whether HIF-1α has an effect on the regulation of survivin gene expression in LSCC cells under hypoxia.

Study design: Prospective, observational.

Setting: Shanghai Jiaotong University Affiliated First People's Hospital.

Subjects and methods: The expression of HIF-1α and survivin protein in human LSCC tissues was analyzed by immunohistochemistry. HIF-1α and survivin gene expression levels in Hep-2 cells were detected by real-time quantitative reverse transcription polymerase chain reaction (RT-PCR) and Western blot under normoxic or hypoxic conditions. In hypoxic cells, HIF-1α expression was inhibited by RNA interference.

Results: HIF-1α and survivin were both highly expressed in LSCC tissues and significantly related to the clinical stage and lymph node metastasis (P < .05). Meanwhile, a positive correlation existed between HIF-1α and survivin expression (r = 0.456, P < .01). In LSCC cells, HIF-1α and survivin expression were obviously upregulated in response to hypoxia (P < .05). The downregulation of HIF-1α expression dramatically decreased survivin gene expression in hypoxic cells (P < .05).

Conclusion: HIF-1α could be considered as an important regulator for the upregulation of survivin gene expression induced by hypoxia in LSCC cells, and both proteins could be regarded as 2 key predictors of malignant progression and metastasis of LSCC.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Analysis of Variance
  • Biomarkers, Tumor / analysis
  • Blotting, Western
  • Carcinoma, Squamous Cell / genetics*
  • Carcinoma, Squamous Cell / pathology
  • Carcinoma, Squamous Cell / surgery
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Hypoxia-Inducible Factor 1, alpha Subunit / genetics*
  • Hypoxia-Inducible Factor 1, alpha Subunit / metabolism
  • Immunohistochemistry
  • Inhibitor of Apoptosis Proteins / genetics*
  • Inhibitor of Apoptosis Proteins / metabolism
  • Laryngeal Neoplasms / genetics*
  • Laryngeal Neoplasms / pathology
  • Laryngeal Neoplasms / surgery
  • Male
  • Middle Aged
  • Retrospective Studies
  • Reverse Transcriptase Polymerase Chain Reaction / methods
  • Sensitivity and Specificity
  • Survival Rate
  • Survivin
  • Tissue Embedding
  • Tumor Cells, Cultured
  • Up-Regulation

Substances

  • BIRC5 protein, human
  • Biomarkers, Tumor
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Inhibitor of Apoptosis Proteins
  • Survivin