Increased expression of genes for basic fibroblast growth factor and transforming growth factor type β2 in human benign prostatic hyperplasia

Mori, Haruo; Maki, Masatoshi; Oishi, Kenji; Jaye, Michael; Igarashi, Koichi; Yoshida, Osamu; Hatanaka, Masakazu

doi:10.1002/pros.2990160108

Cited by 176 publications

(96 citation statements)

References 27 publications

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“…A twofold increase in FGF2 mRNA in BPH tissues has been observed by Mori and colleagues, 21 consistent with the idea that FGF2 expression is controlled primarily by the level of mRNA in vivo. FGF2 transcription is regulated by a variety of factors in different cell types 14 -16 including cytokines.…”

Section: Discussionsupporting

confidence: 87%

Interleukin-8 Is a Paracrine Inducer of Fibroblast Growth Factor 2, a Stromal and Epithelial Growth Factor in Benign Prostatic Hyperplasia

Giri

Ittmann

2001

The American Journal of Pathology

119

103

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Benign prostatic hyperplasia (BPH) is an extremely common disease of older men in which there is benign overgrowth of the prostatic transition zone, leading to obstruction of urine outflow. Fibroblast growth factor (FGF) 2, a potent growth factor for prostatic stromal and epithelial cells, is increased twofold in BPH and its concentration is correlated with stromal proliferation in this condition. Immunohistochemistry of normal and hyperplastic prostate revealed that FGF2-expressing stromal cells were present in higher numbers near the epithelial acini, implying that epithelial cells may express a factor that induces FGF2 expression by stromal cells. Benign prostatic hyperplasia (BPH) is an extremely common condition of older men, such that by 70 years of age the majority of men exhibit clinical symptoms of this disease. 1 The benign growth of the prostatic transition zone that is characteristic of BPH leads to obstruction of urine outflow and in this manner causes considerable morbidity. Thus BPH is of considerable medical importance and yet its pathogenesis is still obscure.Prostate growth is controlled by a variety of polypeptide growth factors, including members of the fibroblast growth factor (FGF) gene family. 2 FGF2, FGF7, and FGF9 are all present in high concentrations in normal human prostate. 3-6 FGF2 is a potent growth factor for prostatic stromal cells. 4,6,7 In addition it can stimulate proliferation of primary prostatic epithelial cells in culture. 5,6 Thus FGF2 can act as both a paracrine growth factor for prostatic epithelial cells and as an autocrine growth factor for prostatic stromal cells.The concentration of both FGF7 4 and FGF2 3,4 are significantly increased in hyperplastic prostate in comparison to normal peripheral and transition zone tissue. FGF2 is a potent mitogen for prostatic stromal cells and quantitative analysis of cellular proliferation by Ki67 immunohistochemistry of frozen sections of the tissue taken before protein extraction revealed a correlation between increased FGF2 tissue concentration and increased proliferation of stromal cells in BPH tissue, 4 consistent with a key role for this growth factor in driving the abnormal stromal proliferation in BPH.Given that FGF2 protein is increased in BPH and that this overexpression has functional consequences for the proliferation of prostatic stromal cells, we sought to determine what factors control FGF2 expression in the human prostate. We report here that interleukin (IL)-8 is produced by prostatic epithelial cells and can act as a paracrine inducer of FGF2 production by prostatic stromal cells in vitro. In addition, we have found that IL-8 is present in substantial quantities in human prostate in vivo and that IL-8 concentration is elevated in BPH tissue. Thus stromal proliferation in BPH is controlled, at least in part, by IL-8 secreted by prostatic epithelial cells. This may ultimately lead to increased tissue mass in the prostatic transition zone, which is critical in the pathogenesis of BPH. Materials and Methods Tissue Acq...

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Section: Discussionsupporting

confidence: 87%

Interleukin-8 Is a Paracrine Inducer of Fibroblast Growth Factor 2, a Stromal and Epithelial Growth Factor in Benign Prostatic Hyperplasia

Giri

Ittmann

2001

The American Journal of Pathology

119

103

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“…They share similar biological properties but present slightly different tissue distribution (Massague, 1990). While TGF-β2 mRNA appears to be increased in BPH (Mori et al, 1990), TGF-β1 mRNA levels have been suggested to be increased in PCA (Merz et al, 1994). Additionally, patients with metastatic PCA displaying high levels of serum IL-6 have also been reported to present increased serum levels of TGF-β1 (Adler et al, 1999).…”

Section: Expression Of Genes Encoding Cytokines In Pca and Bph Tissuesmentioning

confidence: 99%

High expression of indoleamine 2,3-dioxygenase gene in prostate cancer

Feder-Mengus¹,

Wyler²,

Hudolin³

et al. 2008

European Journal of Cancer

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Arginase 2, inducible-and endothelial-nitric-oxide synthase (iNOS and eNOS), indoleamine 2,3-dioxygenase (IDO) and TGF-beta, might impair immune functions in prostate cancer (PCA) patients. However, their expression was not comparatively analysed in PCA and benign prostatic hyperplasia (BPH). We evaluated the expression of these genes in PCA and BPH tissues. Seventy-six patients (42 BPH, 34 PCA) were enrolled. Arginase 2, eNOS and iNOS gene expression was similar in BPH and PCA tissues. TGF-beta1 gene expression was higher in BPH than in PCA tissues (p=0.035). IDO gene expression was more frequently detectable (p=0.00007) and quantitatively higher (p=0.00001) in PCA tissues than in BPH. IDO protein, expressed in endothelial cells from both BPH and PCA, was detectable in tumour cells in PCA showing evidence of high specific gene expression. In these patients, IDO gene expression correlated with kynurenine/tryptophan ratio in sera. Thus high expression of IDO gene is specifically detectable in PCA. 1 High expression of indoleamine 2,3-dioxygenase gene in prostate cancerChantal FEDER-MENGUS 1 * and Stephen WYLER 1 * , Tvrtko HUDOLIN 2 , Robin RUSZAT 1 , Lukas BUBENDORF 3 , Alberto CHIARUGI 4 , Maria PITTELLI 4 , Walter P. Seventy-six patients, 42 BPH and 34 PCA, were enrolled. Expression of arginase 2, eNOS and iNOS genes was similar in BPH and PCA tissues. TGF-β1 gene expression was significantly higher in BPH than in PCA tissues (p=0.035). In contrast IDO gene expression was more frequently detectable in PCA as compared to BPH (p=0.00007). Its extent was also significantly higher in PCA than in BPH (p=0.00001).Immunohistochemistry revealed IDO protein in endothelial cells from both BPH and PCA. However, in PCA showing evidence of high specific gene expression, IDO was detectable in tumor cells as well. In patients bearing these tumors, IDO gene expression correlated with kynurenine/tryptophan ratio in sera.These data indicate that while genes encoding Arginase 2, iNOS, eNOS and TGF-β immunosuppressive factors are expressed in PCA and BPH, high expression of IDO gene is only detectable in PCA.

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“…In BPH, the local concentration of bFGF is two-to threefold higher than in normal prostate (9,10). This fact suggests that bFGF is probably involved in BPH.…”

Section: Introductionmentioning

confidence: 96%

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

Boget

Cereser²,

Parvaz³

et al. 2001

European Journal of Endocrinology

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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 ®broblast growth factors (FGFs), epidermal growth factor and transforming growth factor b. 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 signi®cantly 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.

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Increased expression of genes for basic fibroblast growth factor and transforming growth factor type β2 in human benign prostatic hyperplasia

Cited by 176 publications

References 27 publications

Interleukin-8 Is a Paracrine Inducer of Fibroblast Growth Factor 2, a Stromal and Epithelial Growth Factor in Benign Prostatic Hyperplasia

Interleukin-8 Is a Paracrine Inducer of Fibroblast Growth Factor 2, a Stromal and Epithelial Growth Factor in Benign Prostatic Hyperplasia

High expression of indoleamine 2,3-dioxygenase gene in prostate cancer

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

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