Premium
Dysregulation of Hypoxia Inducible Factor‐1α in Head and Neck Squamous Cell Carcinoma Cell Lines Correlates With Invasive Potential
Author(s) -
Cohen Noam A.,
Lai Stephen Y.,
Ziober Amy F.,
Ziober Barry L.
Publication year - 2004
Publication title -
the laryngoscope
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.181
H-Index - 148
eISSN - 1531-4995
pISSN - 0023-852X
DOI - 10.1097/00005537-200403000-00006
Subject(s) - head and neck squamous cell carcinoma , cancer research , hypoxia (environmental) , hif1a , downregulation and upregulation , cell culture , hypoxia inducible factors , biology , transcription factor , cell , tumor hypoxia , pathology , radiation therapy , medicine , head and neck cancer , angiogenesis , chemistry , gene , biochemistry , genetics , organic chemistry , oxygen
Objectives/Hypothesis Tumor hypoxia appears to be closely associated with tumor propagation, malignant progression, and resistance to radiotherapy. Hypoxia inducible factor‐1α (HIF‐1α) is a transcription factor that is upregulated under hypoxic conditions and activates hypoxic adaptation pathways which include neovascularization, erythropoiesis, and glycolysis. Hypoxia inducible factor‐1α is under tight regulation with undetectable levels of expression in normoxia and robust expression in hypoxia. Mutations that activate oncogenes or inactivate tumor suppressor genes increase the expression of HIF‐1α. Furthermore, it has been demonstrated that HIF‐1α is overexpressed in head and neck squamous cell carcinoma and that the degree of expression has predictive and prognostic significance for patients undergoing radiotherapy. The study investigated whether overexpression of HIF‐1α in head and neck squamous cell carcinoma results from a physiological response to local hypoxia or from oncogenic mutational progression. Study Design Expression of HIF‐1α under normoxic and hypoxic conditions was evaluated in cell lines derived from head and neck squamous cell carcinoma. Cell lines that were used displayed varying degrees of in vitro invasiveness. Methods Hypoxia inducible factor‐1α expression was detected by Western blot analysis. Cells were treated for 3 hours in 1% oxygen, then re‐exposed to normoxia for varying times before lysis and detection of HIF‐1α. Results Under normoxic conditions, HIF‐1α expression was upregulated in invasive cells compared with noninvasive cells, and the degradation of HIF‐1α following a hypoxic stimulus was blunted in invasive cells as compared with noninvasive cells. Conclusion The authors presented evidence that dysregulation of HIF‐1α may play a role in the malignant progression of head and neck squamous cell carcinoma. It is likely that dysregulated expression of the transcription factor HIF‐1α contributes to the invasive properties associated with hypoxia and advanced head and neck squamous cell carcinoma.