Endocrine Abstracts

Background: Tissue hypoxia is a hallmark of rapidly proliferating tumours which most frequently adapt and prosper under low oxygen tension. The transcription factor, HIF-1α, is mediating these effects and induces target genes involved in survival, invasion and resistance to drugs and radiation. No data are available on the functional regulation of HIF-1α in thyroid carcinoma cells.

Methods: Using thyroid carcinoma cells derived from papillary (NPA), follicular (FTC-133) and anaplastic (ARO) carcinomas we investigated whether HIF-1α is expressed in these tumour cells and whether there is a change in HIF-1α activity in response to hypoxia (1% O₂) or anoxia using an oxygen chamber. Proliferation was investigated by WST-1 assay.

Results: HIF-1α is expressed in all 3 tumour cell lines under basal conditions. Decreasing oxygen tensions leads to a dramatic up to 50 fold increase in HIF-1α gene activity when measured by a specific reporter gene assay (HRE) and corresponding to increased protein levels in Western blot analysis. This is associated with increased nuclear staining for HIF-1α using confocal microscopy and with stimulatory effects on cell proliferation.

Conclusion: In summary, HIF-1α is clearly regulated in human thyroid carcinoma cells. With its known modulating function for radiosensitivity it may be of particular interest for optimizing therapy in thyroid carcinomas.