Relationship between expression of genes associated with retinoid interferon induced mortality-19, signal transducer and activators of transcription 3, and myeloid cell leukemia-1 with proliferation and apoptosis of esophageal squamous carcinoma cells

Abstract

Objective To investigate the relationship between the expression of genes associated with retinoid interferon induced mortality-19 (GRIM-19), signal transducer and activators of transcription 3 (STAT3), and myeloid cell leukemia-1 (Mcl-1) with esophageal squamous carcinoma cells proliferation and apoptosis and the possible mechanism. Methods The protein expression of GRIM-19, STAT3, Mcl-1 and proliferation cell nuclear antigen (Ki-67) in 50 cases of esophageal squamous carcinoma tissues, 30 cases of atypical tissue adjacent to carcinoma and 50 cases of normal esophageal mucosa tissues was detected by immunohistochemical streptavidin avidin-peroxidase (SP) method. The mRNA expression of GRIM-19, STAT3, Mcl-1 and Ki-67 in 50 cases of esophageal squamous carcinoma tissues, 30 cases of atypical tissue adjacent to carcinoma and 50 cases of normal esophageal mucosa tissues was detected by in situ hybridization. TdT-mediated deoxyuridine triphosphate (dUTP) nick end labeling (TUNEL) method was applied to examine apoptosis of esophageal squamous carcinoma cells. Results The positive expression rate of GRIM-19 protein and mRNA in esophageal squamous carcinoma tissues was significantly lower than that in atypical hyperplasia tissue adjacent to carcinoma and normal esophageal mucosa (protein: χ2=12.130, P=0.000; mRNA: χ2=11.830, P=0.000). The positive expression rate of STAT3 and Mcl-1 protein and mRNA in esophageal squamous carcinoma tissues was significantly higher than that in atypical hyperplasia tissue adjacent to carcinoma and normal esophageal mucosa (STAT3 protein: χ2=4.910, P=0.000, STAT3 mRNA: χ2=5.410, P=0.000; Mcl-1 protein: χ2=4.970, P=0.000, Mcl-1 mRNA: χ2=5.370, P=0.000). The apoptosis of tumor cells in esophageal squamous carcinoma tissues was associated with the positive expression rate of GRIM-19, STAT3 and Mcl-1. The apoptosis index (AI) in the group of GRIM-19 positive expression was higher than that in the group of GRIM-19 negative expression (F=18.355, P=0.048). The AI in the group of STAT3 positive expression was lower than that in the group of STAT3 negative expression (F=19.003, P=0.036). The AI in the group of Mcl-1 positive expression was lower than that in the group of Mcl-1 negative expression (F=18.225, P=0.044). Conclusion The down-regulation of GRIM-19, and up-regulation of STAT3 and Mcl-1 may promote esophageal squamous cancer cell proliferation, and inhibit esophageal squamous cancer cell apoptosis. Key words: Genes associated with retinoid interferon induced mortality-19; Signal transducer and activators of transcription 3; Myeloid cell leukemia-1; Esophageal squamous carcinoma cells; Apoptosis