Alterations of transforming growth factor beta1 (TGF-beta1) and TGFbeta receptor expressions with progression in Dunning rat prostatic adenocarcinoma sublines.
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.
Wikström
P
P
Department of Urology and Andrology, Umeå University, Sweden.
Lindh
G
G
Bergh
A
A
Damber
J E
JE
D030201:Activin Receptors, Type I; D000230:Adenocarcinoma / Q000235:genetics* / Q000276:immunology*; D000818:Animals; D007150:Immunohistochemistry; D008297:Male; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000276:immunology*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics* / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D051381:Rats; D000077293:Receptor, Transforming Growth Factor-beta Type I; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics* / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016212:Transforming Growth Factor beta / Q000235:genetics* / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D012333:RNA, Messenger; D012334:RNA, Neoplasm; D018125:Receptors, Transforming Growth Factor beta; D016212:Transforming Growth Factor beta; D017346:Protein Serine-Threonine Kinases; D030201:Activin Receptors, Type I; D000077293:Receptor, Transforming Growth Factor-beta Type I; D000077294:Receptor, Transforming Growth Factor-beta Type II; C000625843:Tgfbr1 protein, rat