Cytochrome P450 levels are altered in patients with esophageal squamous-cell carcinoma

Abstract

To investigate the role of cytochrome P450 (CYP) in the carcinogenesis of squamous-cell carcinoma (SCC) in human esophagus by determining expression patterns and protein levels of representative CYPs in esophageal tissue of patients with SCC and controls. mRNA expression of CYP2E1, CYP2C, CYP3A4, and CYP3A5 was determined using RT-PCR in both normal and malignant esophageal tissues of patients with untreated esophageal SCC (n = 21) and in controls (n = 10). Protein levels of CYP2E1, CYP2C8, CYP3A4, and CYP3A5 were measured by Western blot. Within the group of SCC patients, mRNA expression of CYP 3A4 and CYP2C was significantly lower in malignant tissue (-39% and -74%, respectively, P < 0.05) than in normal tissue. Similar results were found in CYP3A4 protein levels. Between groups, CYP3A4, CYP3A5, and CYP2C8 protein concentration was significantly higher in non-malignant tissue of SCC patients (4.8-, 2.9-, and 1.9-fold elevation, P < 0.05) than in controls. In contrast, CYP2E1 protein levels were significantly higher in controls than in SCC patients (+46%, P < 0.05). Significant differences exist in protein levels of certain CYPs in non-malignant esophageal tissue (e.g. CYP2C8, CYP3A4, CYP3A5, and CYP2E1) between SCC patients and healthy subjects and may contribute to the development of SCC in the esophagus.