Dysregulation of transforming growth factor-beta 1 expression in N-nitrosomethylbenzylamine-induced rat esophageal tumorigenesis

Alterations in the expression of transforming growth factor-beta 1 (TGF-beta 1) have been implicated for malignancies of both human and experimental animal models. To further investigate the role of TGF-beta 1 in chemically-induced esophageal tumorigenesis, the expression of TGF-beta 1 was analyzed by reverse transcription-polymerase chain reaction (T-PCR) and immunohistochemical studies in N-nitrosomethylbenzylamine (NMBA)-induced rat esophageal tumorigenesis. We observed no significant difference in TGF-beta 1 mRNA levels between 25-week papillomas and normal rat esophageal epithelium. However, TGF-beta 1 mRNA levels were increased 2.9-fold (p<0.05) in 45-week papillomas induced by NMBA, when compared to normal rat esophageal epithelium. Immunohistochemical studies revealed a decreased intracellular TGF-beta 1 immunoreactivity in the papillomas when compared to the normal rat esophageal epithelium, indicating the existence of a discordance between TGF-beta 1 mRNA and protein expression. Furthermore, by immunohistochemical staining of proliferating cell nuclear antigen (PCNA), a predominantely mutually exclusive staining pattern was observed for TGF-beta 1 and PCNA. These findings suggest that overexpression of TGF-beta 1 mRNA occurs late in NMBA-induced rat esophageal tumorigenesis, and the discordant mRNA and protein expression may result in tumor evasion from TGF-beta 1 controlled negative growth regulation, thus promoting tumor progression in this model.