Role of hypoxia and embryonic stem cell genes in head and neck cancers

Purpose: The aim of this study was to determine the effect of hypoxia on HIF-1α, HIF-2α, SOX2, OCT4, NANOG, CD133, ESRRA genes in Hep-2 laryngeal and FaDu pharyngeal cancer cell lines. Materials and Methods: Hep-2 and FaDu cell lines were exposed to hypoxia for 6, 12, 24, 48, and 72 hours to determine the effect of hypoxia and then treated with 5μM, 10μM and 20μM XCT790 under hypoxic conditions. Taqman Gene Expression Assays were used to determine mRNA expressions. Results: In the hypoxic environment, we observed that HIF-2α, SOX2, OCT4, NANOG, CD133, and ESRRA mRNA expressions increased, except HIF-1α in Hep-2 cells. In FaDu cells, it was observed that HIF-1α and SOX2 mRNA expressions decreased, while HIF-2α, OCT4, NANOG, CD133, and ESRRA mRNA expressions increased. When cells were treated with the ESRRA inverse agonist XCT790, the hypoxia-induced gene expression profile was found altered. Conclusion: In our study, it was determined that hypoxia changed the gene expression profile in Hep-2 and FaDu cell lines. According to our results, it was concluded that the ESRRA gene may be an important cofactor of the hypoxic response, but its inhibition alone may not be sufficient to abolish the hypoxic response. Protein data is needed to reveal the precise mechanisms of ESRRA and hypoxia association in head and neck cancers.