Caracterização da expressão gênica dos receptores colinérgicos nicotínicos (CHRNs) no epitélio esofágico normal e em carcinoma epidermóide de esôfago

Abstract

Esophageal cancer (EC) is an extremely aggressive disease and it is one of the most incident and lethal cancers in the world and in Brazil. Esophageal squamous cell carcinoma (ESCC) is the main histological type of EC, being associated with alcohol and tobacco consumptiom. In Western countries, the concomitant use of these two factors provides a multiplying risk for the development of ESCC, and smoking seems to play an important role in both tumor initiation and promotion, while alcohol seems to have a more important role in promoting the tumor. Tobacco s components like nicotine and nitrosamines are powerful carcinogens as well as high-affinity agonists of nicotinic cholinergic receptors (CHRNs). The activation of CHRNs by tobacco components results in the activation of key cellular signaling pathways for cancer progression. Very little is known about the expression and regulation of CHRNs in esophageal mucosa and carcinogenesis process. Thus, the objective of this study was to analyze the expression of CHRNs subunits in healthy esophageal mucosa and ESCC. Furthermore, we aimed to investigate whether etiologic factors associated with ESCC development could affect the expression of these receptors. According to our results, α3, α5, α7 and β4 subunits are expressed in human normal esophagus whereas α1, α4, α9 e α10 subunits showed very low or no expression in the same tissue. Besides, there were differences in the expression of α3 and α7 subunits in alcoholic and smokers when compared with non- alcoholic (α3 subunit) and nonsmokers (α7 subunit). Regarding ESCC analyses, CHRNA5 and CHRNA7 were found overexpressed in tumor tissues when compared to surrounding mucosa. There were differences in the expression of α7 subunit in tumor tissues compared to healthy tissue and of β4 subunit in tumor tissue and surrounding mucosa compared to healthy tissue. No differences were found in the expressions of these subunits in esophageal cancer cell lines exposed to nicotine or ethanol. These results suggest that CHRNs play a role in esophageal physiology and that ESCC etiological factors seem to be able to affect the expression of these receptors.