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.

Transforming growth factor-beta attenuates ischemia-induced alterations in cerebrovascular responses

1993 ◽  
Vol 264 (2) ◽  
pp. H381-H385 ◽  
Author(s):  
W. M. Armstead ◽  
R. Mirro ◽  
S. L. Zuckerman ◽  
M. Shibata ◽  
C. W. Leffler
Keyword(s):  
Cerebrospinal Fluid ◽  
Cerebral Ischemia ◽  
Growth Factor ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Ischemia Reperfusion ◽  
Fold Increase ◽  
Tgf Beta ◽  
Before And After ◽  
Growth Factor Beta

We observed previously that 20 min of global cerebral ischemia followed by 45 min of reperfusion selectively blocked cerebral vasodilation to hypercapnia and hypotension. This study determines the effects of pretreatment with transforming growth factor-beta (TGF-beta) on cerebrovascular responses after cerebral ischemia in piglets equipped with closed cranial windows. Hypercapnia-induced pial arteriolar dilation was blocked after cerebral ischemia (20 +/- 1 vs. 2 +/- 1% dilation before and after ischemia, respectively). Similarly, the increases in periarachnoid cortical cerebrospinal fluid 6-ketoprostaglandin F1 alpha (6-keto-PGF1 alpha) and prostaglandin E2 (PGE2) concentration in response to hypercapnia were blocked (2.5 +/- 0.2- vs. 0.2 +/- 0.4-fold and 2.1 +/- 0.1- vs. 0.3 +/- 0.4-fold increase in 6-keto-PGF1 alpha and PGE2, respectively). Treatment with topical TGF-beta (400 ng/ml) before and during ischemia-reperfusion attenuated the loss of hypercapnia-induced cerebrovascular dilation (20 +/- 1 vs. 14 +/- 1% dilation before and after ischemia, respectively) and the loss of associated changes in cerebrospinal fluid prostanoids (2.0 +/- 0.2- vs. 1.7 +/- 0.2-fold and 2.3 +/- 0.2- vs. 2.2 +/- 0.3-fold increase in 6-keto-PGF1 alpha and PGE2 before and after ischemia, respectively). The loss of cerebrovascular dilation in response to hemorrhagic hypotension after ischemia was similarly prevented by TGF-beta. Cerebrovascular dilation to topical isoproterenol was unchanged after ischemia. TGF-beta may preserve endothelial cell function. We conclude that topical TGF-beta can attenuate cerebromicrovascular compromise caused by ischemia-reperfusion in newborn pigs.

scholarly journals Fibroblast growth factor receptor 1 (FGFR1) is over-expressed in benign prostatic hyperplasia whereas FGFR2-IIIc and FGFR3 are not

2001 ◽  
pp. 303-310 ◽  
Author(s):  
S Boget ◽  
C Cereser ◽  
P Parvaz ◽  
A Leriche ◽  
A Revol
Keyword(s):  
Growth Factors ◽  
Benign Prostatic Hyperplasia ◽  
Growth Factor ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Growth Factor Receptor ◽  
Prostatic Hyperplasia ◽  
Fibroblast Growth ◽  
Normal Prostate ◽  
Over Expression

OBJECTIVE: Benign prostatic hyperplasia (BPH) is one of the major public health problems among men: 50% of men over 55 are concerned with this disease. Prostate growth is under the control of androgens which act by means of several growth factors such as fibroblast growth factors (FGFs), epidermal growth factor and transforming growth factor beta. Basic FGF (bFGF) has been shown to stimulate prostatic stromal growth. In BPH, bFGF concentration is two- to threefold higher than in normal prostate. In this work, the bFGF receptors (FGFR1, FGFR2-IIIc and FGFR3) genes expression was evaluated to study the correlation between the expression of bFGF receptors and induction of BPH. METHODS: The expression of FGFRs was analyzed by RT-PCR, FGFR1 was localized by immunohistochemistry and protein expression was evaluated by Western blot. RESULTS: A two- to eightfold over-expression of FGFR1 was observed in BPH compared with normal prostates. FGFR1 was localized in the stroma both in BPH and in normal prostates and 1.5- to 2.5-fold over-expression of the protein was observed. The expression of FGFR2-IIIc and FGFR3, more secondary receptors, was not significantly different between BPH and normal prostates. CONCLUSIONS: bFGF receptors and particularly FGFR1 seem to be involved in the induction and evolution of BPH and probably potentiate bFGF over-expression effects in BPH.

Laryngeal keratinocytes show variable inhibition of replication by TGF-beta

1990 ◽  
Vol 96 (1) ◽  
pp. 115-119
Author(s):  
T.P. DiLorenzo ◽  
B.M. Steinberg
Keyword(s):  
Growth Factor ◽  
Epithelial Cells ◽  
Growth Inhibition ◽  
Cell Density ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Marked Variation ◽  
Tgf Beta ◽  
High Calcium ◽  
Growth Factor Beta

The response of secondary human laryngeal epithelial cells to transforming growth factor-beta (TGF-beta) was investigated, and this response was compared with that of epithelial cells derived from virally induced laryngeal papillomas. In most cases, both normal laryngeal epithelial cells and those derived from laryngeal papillomas exhibited growth inhibition in response to 10 ng ml-1 TGF-beta. Response was not a function of cell density or proliferation rate when cells were in a low-calcium medium, but was reduced in high calcium. Using keratinocytes derived from several different tissue explants, we found that cells grown from different explants show marked variation in response to TGF-beta.

A phorbol ester-regulated ribonuclease system controlling transforming growth factor beta 1 gene expression in hematopoietic cells

1990 ◽  
Vol 10 (11) ◽  
pp. 5983-5990
Author(s):  
R E Wager ◽  
R K Assoian
Keyword(s):  
Gene Expression ◽  
Growth Factor ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Fold Increase ◽  
Mrna Levels ◽  
Tgf Beta ◽  
Growth Factor Beta

12-Tetradecanoylphorbol-13-acetate (TPA)-induced differentiation of U937 promonocytes leads to a 30-fold increase in transforming growth factor beta 1 (TGF-beta 1) gene expression, and this effect results from a stabilized mRNA. Similar up-regulation was detected in TPA-treated K562 erythroblasts but was absent from cell lines that do not differentiate in response to TPA. Related studies in vitro showed that postnuclear extracts of U937 promonocytes contain a ribonuclease system that degrades TGF-beta 1 mRNA selectively and that this system is completely blocked by prior treatment of the cells with TPA. These data identify a new mechanism for regulating TGF-beta 1 mRNA levels and allow us to establish the overall basis for control of TGF-beta 1 gene expression by activation of protein kinase C. Our results also provide a new basis for understanding the long-term up-regulation of TGF-beta 1 gene expression that can accompany hematopoietic cell differentiation.

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