Expression of transforming growth factor beta1 and its type II receptor in mouse colon tumors induced by azoxymethane.

Alterations in transforming growth factor beta1 (TGF-beta1) and its type II receptor (TbetaR-II) have been implicated in the pathogenesis of a variety of human cancers and animal tumor models. We postulated that TGF-beta1 and TbetaR-II alterations may also be involved in mouse colon tumorigenesis induced by the chemical carcinogen, azoxymethane (AOM). In the present study, normal colon tissues and AOM-induced colon tumors from SWR/J mice were analyzed for mutational changes in the TbetaR-II gene, and the expression and localization of TGF-beta1 and TbetaR-II were examined by reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemisty. Direct DNA sequencing of the coding sequence of the TbetaR-II gene revealed no mutational changes in tumors induced by AOM when compared with the sequence from normal colon tissue. However, TGF-beta1 and TbetaR-II mRNA levels in tumor samples were increased 1.8-fold (p<0.01) and 1.3-fold (p<0.01), respectively, when compared with control mouse colon tissue. The results of immunohistochemical analysis of TGF-beta1 and TbetaR-II were correlated with mRNA expression data. An increase in staining intensity of both TGF-beta and TbetaR-II were observed in colon tumors. These findings suggest that alterations in the expression of TGF-beta1 and TbetaR-II may be involved in the pathogenesis of colon tumors induced by AOM in mice.