Expression of transforming growth factors beta-1, beta 2 and beta 3 in human bladder carcinomas.
We previously detected elevated transforming growth factor beta-1 (TGF-beta1) serum levels in patients with invasive bladder carcinomas. In this study, we therefore investigated whether elevated serum levels correlate with enhanced TGF-beta expression in human bladder tumours. mRNA levels of TGF-beta1, -beta2 and -beta3 were reduced in bladder tumour tissue to 86%, 68% and 56%, respectively, of the levels in normal urothelium. On the other hand, TGF-beta1 protein levels were found to be higher in superficial tumours (Ta-T1) (mean level of 0.153 ng mg(-1)) and in invasive T2/T3 tumours (mean level of 0.104 ng mg(-1)) compared with normal urothelium (mean level of 0.065 ng mg(-1)). Invasive T4 tumours, however, contained only low amounts of TGF-beta1 (mean level of 0.02 ng mg(-1)). Neither in mean nor in individual patients were serum and tissue TGF-beta levels correlated with each other. Cell culture experiments on primary bladder cells revealed a 57% decrease in TGF-beta1 mRNA levels in tumour compared with normal epithelial cells. Tumour epithelial cells contained about two times higher levels of TGF-beta2 and TGF-beta3 mRNA than normal epithelial cells. Fibroblasts expressed about the same amount of TGF-beta1 or TGF-beta2 as epithelial cells. Yet, fibroblasts released only 19% and 13% of the amount secreted by tumour epithelial cells into the supernatant. TGF-beta3, on the other hand, was expressed by fibroblasts with higher levels than by epithelial cells. TGF-beta1 was the predominent isoform in bladder tissue and cells at protein as well as on mRNA levels indicating that TGFs-beta2 and -beta3 are of minor importance in bladder cancer. In summary, there is a lack of correlation between TGF-beta serum levels and TGF-beta expression in tumour tissue in bladder cancer.
Eder
I E
IE
Department of Urology, University of Innsbruck, Austria.
Stenzl
A
A
Hobisch
A
A
Cronauer
M V
MV
Bartsch
G
G
Klocker
H
H
D001483:Base Sequence; D002295:Carcinoma, Transitional Cell / Q000097:blood / Q000235:genetics* / Q000378:metabolism; D002478:Cells, Cultured; D015653:Cystectomy; D003627:Data Interpretation, Statistical; D004797:Enzyme-Linked Immunosorbent Assay; D004847:Epithelial Cells; D005347:Fibroblasts / Q000166:cytology; D006801:Humans; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis*; D016212:Transforming Growth Factor beta / Q000032:analysis / Q000097:blood / Q000235:genetics*; D014407:Tumor Cells, Cultured; D001743:Urinary Bladder / Q000166:cytology / Q000378:metabolism; D001749:Urinary Bladder Neoplasms / Q000097:blood / Q000235:genetics* / Q000378:metabolism; D019459:Urothelium / Q000166:cytology / Q000378:metabolism
D012333:RNA, Messenger; D016212:Transforming Growth Factor beta