Transforming growth factor-beta1 (TGF-beta1) inhibits epithelial cell proliferation in the normal prostate. Prostate tumours express high levels of TGF-beta1, and seem to acquire resistance to its anti-proliferative effects with tumour progression. In this study, TGFbeta variations with tumour progression were examined in the Dunning prostatic adenocarcinoma model. Expression of TGF-beta1 and TGFbeta receptor type I and type II (TGFbeta-RI and TGFbeta-RII) in rat dorsolateral prostate (DLP) and Dunning tumour sublines (PAP, AT-1, AT-2, AT-3 and MatLyLu) was examined in vitro and in vivo, using competitive reverse transcription-polymerase chain reaction (RT-PCR), Northern and Western blot, and immunohistochemistry. All tumours expressed elevated levels of TGF-beta1 and TGFbeta-RI mRNA, when compared with the DLP (P < or = 0.05). All tumours except MatLyLu also expressed elevated levels of TGFbeta-RII mRNA (P < or = 0.05). Interestingly, TGFbeta-RII protein levels were very low in the highly metastatic AT-3 and MatLyLu tumours in vivo, when compared with levels in the PAP, AT-1, and AT-2 tumours. This difference was not detected for the AT-1, AT-2, and AT-3 cells in vitro. Immunostaining of TGF-beta1, TGFbeta-RI, and TGFbeta-RII was localised principally in normal and tumour epithelial cells, and occasionally in smooth muscle cells. In conclusion, high expression of TGF-beta1 and TGFbeta-RI and low expression of TGFbeta-RII may contribute to tumour progression and metastasis in the Dunning prostatic adenocarcinoma model.
1999. Vol. 27, no 3, 185-93 p.