Role of retinoic acid receptors in squamous-cell carcinoma in human esophagus

BACKGROUND Worldwide, cancer in the esophagus ranks among the 10 most common cancers. Alterations of retinoic acid receptors (e.g. RARalpha, beta, gamma, and RXRalpha, beta, gamma) expression is considered to play an important role in development of squamous-cell carcinoma (SCC), which is the most common esophageal cancer. Alcohol consumption and smoking, which can alter retinoic acid receptor levels, have been identified as key risk factors in the development of carcinoma in the aero-digestive tract. Therefore, the aim of the present study was to evaluate protein levels of retinoic acid receptors (i.e. RARalpha, beta, gamma, and RXRbeta) in esophageal SCC and surrounding normal tissue of patients with untreated SCC and controls. METHODS All study participants completed a questionnaire concerning smoking and alcohol drinking habits as well as anthropometrical parameters. Protein levels of RARalpha, beta, gamma, and RXRbeta were determined by Western Blot in normal esophageal tissue and tissue obtained from SCC of 21 patients with newly diagnosed esophageal SCC and normal esophageal tissue of 10 controls. RESULTS Protein levels of RARgamma were significantly lower by approximately 68% in SCC compared to normal surrounding tissue in patients with SCC that smoked and/or consumed elevated amounts of alcohol. Furthermore, RARalpha protein levels were significantly lower (approximately- 45%) in SCC in comparison to normal esophageal mucosa in patients with elevated alcohol intake. When comparing protein levels of retinoic acid receptors between normal tissue of patients with SCC and controls, RARgamma protein levels were found to be significantly higher (approximately 2.7-fold) in normal esophageal tissue of SCC patients than in esophageal tissue obtained from controls. No differences were found for RARalpha, beta, and RXRbeta protein levels between normal esophageal tissue of patients and that of controls. CONCLUSION In conclusion, results of the present study suggest that alterations of retinoic acid receptors protein may contribute in the development of SCC in esophagus and that in some patients life style (e.g. smoking and alcohol consumption) may be a critical component in the alteration of retinoic acid receptor levels in esophagus.