Alterations of transforming growth factor β1 (TGF-β1) and TGFβ receptor expressions with progression in Dunning rat prostatic adenocarcinoma sublines

Transforming growth factor-beta 1 (TGF-beta 1) inhibits epithelial cell proliferation in the normal prostate. Prostate tumours express high levels of TGF-beta 1, and seem to acquire resistance to its anti-proliferative effects with tumour progression. In this study, TGF beta variations with tumour progression were examined in the Dunning prostatic adenocarcinoma model. Expression of TGF-beta 1 and TGF beta receptor type I and type II (TGF beta-RI and TGF beta-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-beta 1 and TGF beta-RI mRNA, when compared with the DLP (P less than or equal to 0.05). All rumours except MatLyLu also expressed elevated levels of TGF beta-RII mRNA (P less than or equal to 0.05). Interestingly, TGF beta-RII protein levels were very low in the highly metastatic AT-3 and MatLyLu rumours in vivo, when compared with levels in the PAP, AT-1, and AT-2 rumours. This difference was not detected for the AT-1, AT-2, and AT-3 cells in vitro. Immunostaining of TGF-beta 1, TGF beta-RI, and TGF beta-RII was localised principally in normal and tumour epithelial cells, and occasionally in smooth muscle cells. In conclusion, high expression of TGF-beta 1 and TGF beta-RI and low expression of TGF beta-RII may contribute to tumour progression and metastasis in the Dunning prostatic adenocarcinoma model.