The role of hypoxia and embryonic stem cell genes in laryngeal cancer pathogenesis

Laryngeal cancer accounts for about 25% of head and neck cancers and is usually seen in men of middle or older age. More than 90% of laryngeal cancers are squamous-cell cancers. One of the most common features of solid tumors and one of the major environmental stresses is hypoxia. The reduction of the oxygen concentration below the physiological level, promotes maintanance and self-renewal of the human embryonic stem cells, and reducing spontaneous differentiation in vitro. Similarities between stem cell and cancer cells suggest that both groups may use common pathways in the regulation of gene expression. Twenty six patients with squamous cell laryngeal carcinoma who were diagnosed at University of Cukurova Medical School, Department of Otolaryngolgy were included in this study. RNA isolation from tissues was performed to compare the expression levels of hypoxia inducible factors and embryonic stem cell genes in tumor and normal tissues. In our study, it was determined that the expression of HIF-1α, OCT4 and NANOG genes were increased in tumor tissues compared to normal tissues. Furthermore, for determining the effect of hypoxia on HIF-1α, HIF-2α SOX2, OCT4, NANOG, CD133, ESRRA genes, Hep2 larynx cancer and FaDu pharynx cancer cell lines were exposed to hypoxia. In our study, mRNA expressions of HIF-1α, HIF-2α, SOX2, OCT4, NANOG, CD133 and ESRRA genes were elevated in hypoxia-exposed Hep-2 cells, in hypoxia exposed FaDu cells, mRNA expression of HIF-1α and SOX2 were decreased, HIF-2α, OCT4, NANOG, CD133 and ESRRA mRNA expressions were increased. When cells were treated with the ESRRA inhibitor XCT790, hypoxia-induced gene expression profiles were changed. Our study provides a new approach to develop new strategies in reducing the effect of hypoxia in the treatment of larynx cancer. Key Words: Larynx cancer, hypoxia, embryonic stem cell genes, Real Time-PCR