Transforming growth factor-β3 is expressed in nondividing basal epithelial cells in normal human prostate and benign prostatic hyperplasia, and is no longer detectable in prostate carcinoma

The Prostate ◽  
1997 ◽  
Vol 31 (2) ◽  
pp. 103-109 ◽  
Author(s):  
Valentin Djonov ◽  
Roland K. Ball ◽  
Simon Graf ◽  
Alain E. Mottaz ◽  
Anne-Marie Arnold ◽  
...  
Keyword(s):  
Benign Prostatic Hyperplasia ◽  
Growth Factor ◽  
Epithelial Cells ◽  
Prostate Carcinoma ◽  
Transforming Growth Factor ◽  
Prostatic Hyperplasia ◽  
Human Prostate ◽  
Normal Human ◽  
Basal Epithelial Cells

scholarly journals Localization of Transforming Growth Factor-β1 and Type II Receptor in Developing Normal Human Prostate and Carcinoma Tissues

1998 ◽  
Vol 46 (3) ◽  
pp. 379-388 ◽  
Author(s):  
Michael J. Gerdes ◽  
Melinda Larsen ◽  
Lauren McBride ◽  
Truong D. Dang ◽  
Bing Lu ◽  
...  
Keyword(s):  
Growth Factor ◽  
Epithelial Cells ◽  
Prostate Carcinoma ◽  
Stromal Cells ◽  
Transforming Growth Factor ◽  
Carcinoma Cells ◽  
Human Prostate ◽  
Type Ii ◽  
Normal Prostate ◽  
Normal Human

Transforming growth factor-β1 (TGF-β1) is implicated in prostate development, and elevated expression of TGF-β1 has been correlated with prostate carcinogenesis. In this study, cell type specificity of TGF-β1 and TGF-β receptor Type II (RcII) protein expression was determined by immunocytochemistry in human normal prostate and compared to prostate carcinoma tissues. Heterogeneous localization patterns of LAP-TGF-β1 (TGF-β1 precursor) and RcII were observed in both epithelial and mesenchymal cells in fetal prostate, with LAP-TGF-β1 localizing to more basal epithelial cells. Homogeneity of LAP-TGF-β1 staining was increased in neonatal, prepubertal, and adult prostate, with elevated immunoreac-tivity noted in epithelial acini relative to stromal tissue for both LAP-TGF-β1 and RcII proteins. In stromal tissues, RcII cell localization exhibited staining patterns nearly identical to smooth muscle α-actin. In prostate carcinoma, LAP-TGF-β1 localized to carcinoma cells with an increased staining heterogeneity relative to normal prostate. In contrast to normal epithelial cells, carcinoma epithelial cells exhibited low to nondetectable RcII staining. Stromal cell staining patterns for LAP-TGF-β1 and RcII in carcinoma, however, were identical to those of normal prostate stromal cells. These studies implicate both epithelial and stromal cells as sites of TGF-β1 synthesis and RcII localization in the developing and adult normal human prostate. In addition, these data indicate a loss of epithelial expression of RcII concurrent with altered LAP-TGF-β1 expression in human prostate carcinoma cells.

scholarly journals Transforming growth factor-beta induces growth inhibition and IGF-binding protein-3 production in prostatic stromal cells: abnormalities in cells cultured from benign prostatic hyperplasia tissues

2000 ◽  
Vol 164 (2) ◽  
pp. 215-223 ◽  
Author(s):  
P Cohen ◽  
SE Nunn ◽  
DM Peehl
Keyword(s):  
Benign Prostatic Hyperplasia ◽  
Growth Factor ◽  
Growth Inhibition ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Fold Increase ◽  
Prostatic Hyperplasia ◽  
Igf Binding ◽  
Growth Factor Beta ◽  
Igfbp 3

The IGF axis has been implicated in the pathogenesis of benign prostatic hyperplasia (BPH) via the paracrine action of IGFs and IGF-binding proteins (IGFBPs). In this study, we examined the regulation of cell growth and IGFBP-3 secretion by transforming growth factor-beta (TGF-beta) in prostatic stromal cell (PC-S) cultures from histologically normal tissues and tissues from BPH. PC-S cultures were treated with varying doses of TGF-beta1. Forty-eight hour conditioned media (CM) from these cultures were subjected to Western immunoblotting and ligand blotting for detection and quantification of IGFBPs. IGFBPs-2, -3 and -4 were detected in the CM from normal PC-S cultures. In CM from BPH PC-S, IGFBP-3 levels were 2-fold lower at baseline than in the normal PC-S CM, in addition to the differences in IGFBPs-2 and -5 which we have previously reported. In response to TGF-beta1, a 15-fold increase in the levels of IGFBP-3 was observed in normal PC-S CM, while a mere 2-fold increase was observed in BPH PC-S CM (P<0.001). These findings were confirmed by specific immunoblotting and immunocytochemistry. IGFBP-3 mRNA levels detected by Northern blotting of total RNA extracted from similar cultures showed the induction of IGFBP-3 expression by TGF-beta1 in normal PC-S and its lack of induction in BPH PC-S. Cell growth inhibition in response to TGF-beta1 correlated with the IGFBP-3 concentrations found in CM. Normal PC-S showed a 60% decrease in cell number after 10 days in media with 1 ng/ml TGF-beta1, compared with the untreated control. The decrease in proliferation observed in comparably treated BPH cells was only 20% (P<0.001). In conclusion, BPH PC-S had a reduced IGFBP-3 response to TGF-beta1 and demonstrated decreased TGF-beta1-induced growth inhibition relative to normal PC-S. We hypothesize that in normal PC-S, TGF-beta exerts its anti-proliferative effects by stimulating the production of IGFBP-3, which acts as an inhibitory factor, either by inhibiting IGFs or directly by interacting with cells, and that this process is altered in BPH PC-S.

Sign in / Sign up

Export Citation Format

Share Document