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Abstract

BackgroundWorldwide, cancer in the esophagus ranks among the 10 most common cancers. Alterations of retinoic acid receptors (e.g. RARα, β, γ, and RXRα, β, γ) 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. RARα, β, γ, and RXRβ) in esophageal SCC and surrounding normal tissue of patients with untreated SCC and controls.MethodsAll study participants completed a questionnaire concerning smoking and alcohol drinking habits as well as anthropometrical parameters. Protein levels of RARα, β, γ, and RXRβ 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.ResultsProtein levels of RARγ were significantly lower by ~68% in SCC compared to normal surrounding tissue in patients with SCC that smoked and/or consumed elevated amounts of alcohol. Furthermore, RARα protein levels were significantly lower (~- 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, RARγ protein levels were found to be significantly higher (~2.7-fold) in normal esophageal tissue of SCC patients than in esophageal tissue obtained from controls. No differences were found for RARα, β, and RXRβ protein levels between normal esophageal tissue of patients and that of controls.ConclusionIn 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.

Risk Factors of Esophageal Squamous Cell Carcinoma beyond Alcohol and Smoking

“…Five studies focused on mechanistic pathways and end metabolites in ESCC identified pathways of interest, namely: Prostaglandin E2 (PGE 2 ), acetaldehyde, and retinoid metabolism [ 53 , 54 , 55 , 56 ]. PGE 2 plays a central role in the Sammon and Alderson model of esophageal carcinogenesis described in 1998 [ 57 ].…”

“…These have been proposed to be a risk factor of ESCC. Diminished abundance of retinoic acid receptors through a ‘functional’ down-regulation of mRNA expression is associated with an increased risk of ESCC [ 56 ].…”

Association of Retinoic Acid Receptors with Extracellular Matrix Accumulation in Rats with Renal Interstitial Fibrosis Disease

“…RARα and RARβ appear at early stages of human embryonic development, and their expression is restricted to certain types of tissues [3]. In the past decades, there were lots of studies reporting that alterations of RARs expressions were associated with the development of some diseases, such as squamous-cell carcinoma [4], mammary carcinomas [5], esophageal cancer [6], etc. However, the role of RARs is complicated, and the mechanisms of RARs in the progression of diseases are not elucidated.…”