Characteristics of FGF-receptors Expressed by Stromal and Epithelial Cells Cultured from Normal and Hyperplastic Prostates

Story, Michael T.; Hopp, Kathleen A.; Molter, Mary; Meier, Daniel A.

doi:10.3109/08977199409010993

Cited by 52 publications

(45 citation statements)

References 39 publications

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“…This suggests that FGF8, commonly secreted by epithelial cells, interacts with stromal tissue in a paracrine fashion. The prostate is known to express FGFR1, 2 and 3, while FGFR4 has only been detected at low levels in prostate cancer cell lines (Story et al, 1994;Ittman and Mansukhani, 1997;Giri et al, 1999;Ropiquet et al, 2000). In prostate carcinogenesis, FGFR splicing characteristics are known to be altered.…”

Section: Discussionmentioning

confidence: 99%

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FGF8 isoform b expression in human prostate cancer

et al. 2003

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Overexpression of fibroblast growth factor 8 (FGF8) mRNA has been previously described in prostate cancer. Of its four isoforms, FGF8b is thought to be the most important in carcinogenesis. We hypothesised that immunodetection of FGF8b in archival prostate cancer specimens is of potential prognostic value. Using a selected cohort of prostate tumours from transurethral (n ¼ 30) and radical prostatectomies (n ¼ 59), an optimised protocol for FGF8b immunoreactivity was used to corroborate expression with clinical parameters. No expression was observed in benign prostates (n ¼ 10). In prostate cancer, immunoreactivity was localised to the malignant epithelium with weak signals in the adjacent stroma. Expression of FGF8b in stage T1 and T2 cancers were 40 and 67%, respectively. In contrast, FGF8b expression was present in 94% of T3 and 100% of T4 cancers. By histological grade, FGF8b was found in 41% of low-grade cancers (Gleason score 4 -6), 60% of intermediate-grade cancers (Gleason score 7 and 92% of high-grade cancers (Gleason score 8 -10). The intensity of expression was significantly associated with stage (P ¼ 0.0004) and grade (Po0.0001) of disease. We further hypothesised that FGF8b overexpression resulted from enhanced transcription and translation rather than from abnormalities involving the FGF8 gene locus. This was tested by means of fluorescent in situ hybridisation in 20 cancer specimens to map the FGF8 gene locus. FGF8 gene copy number in benign and malignant nuclei was found to be similar (2.3370.57 and 2.070.81, respectively P ¼ 0.51). Based on these findings, we propose a multicentre study on cohorts of patients to further evaluate FGF8b as a potential prognostic marker in prostate cancer.

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Section: Discussionmentioning

confidence: 99%

“…It is possible that FGF8b, secreted by epithelial ×1000 ×1000 ×1000 ×2000 ×2000 (Story et al, 1994). Immunohistochemistry demonstrated that FGF8b protein was significantly overexpressed in locally advanced and high-grade tumours.…”

Section: Discussionmentioning

confidence: 99%

FGF8 isoform b expression in human prostate cancer

et al. 2003

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“…14 The FGF family members are mitogenic to both prostatic epithelial and stromal cells. 39 bFGF is produced mainly by stromal and, to a lesser extent, by epithelial cells 36,40 and participates in prostate growth regulation through an autocrine effect on stromal cells and a weak paracrine effect on epithelial cells. 41 Although FGF's role in BPH development is indisputable, it is still unknown at which stage(s) of BPH development bFGF exerts its effects.…”

Section: Discussionmentioning

confidence: 99%

Terazosin treatment suppresses basic fibroblast growth factor expression in the rat ventral prostate

Mitropoulos

Kyroudi-Voulgari²,

Christelli³

et al. 2009

CIM

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Purpose: Alpha1-adrenergic receptor antagonists may not act solely on smooth muscle contractility. We evaluated the in vivo effect of the alpha1 blocker, terazosin, on the expression of basic fibroblast growth factor (bFGF) in the rat ventral prostate. Methods: Wistar rats were treated with terazosin (1.2 mg/ kg body weight, po, every second day) for 120 days. The expression of bFGF was assessed immuno-histochemically in tissue sections and by Western blotting in whole tissue preparations. Results: Terazosin treatment did not affect prostate weight or histomorphology. In the control group, epithelial and stromal cells demonstrated positive staining for the antibFGF antibody. In contrast, the same staining in terazosintreated specimens was either absent or extremely weak. An analogous difference was observed among the corresponding immunoblots. Conclusions: These findings implicate the reduction of bFGF expression by terazosin as a potential additional molecular mechanism of its action that may include alterations in peptide growth factor mediated prostate homeostasis.Drugs that block the action of sympathetic neurotransmitters on 1-adrenergic receptors ( 1-ADRs) are widely used for the treatment of patients with benign prostate hyperplasia (BPH)-related lower urinary tract symptoms. The rationale for their use stems is that they effectively relax prostate smooth muscles, 1 which represent approximately 40% of the cellular volume in hyperplastic glands. 2 The biological effects of extrinsic factors such as hormones and other endocrine-related agents on the prostate are mediated by various peptide growth factors produced by the gland and influence prostate growth, differentiation and function by promoting inter-and intracellular signaling between and within cell populations, through paracrine, autocrine and intracrine effects. 3 Data from several studies indicate that 1-ADR antagonists may not act solely on smooth muscle contractility. Intact autonomic innervation of the rat ventral prostate is necessary to maintain its structural and functional integrity. [4][5][6] Administration of the sympathomimetic phenylephrine induces ventral prostate hyperplasia associated with reduced rates of cellular apoptosis, but not with increased rates of cellular proliferation. 7 Moreover, rapid proliferation of prostatic epithelial cells has been seen in the spontaneously hypertensive rat, 8 an animal model with in-ORIGINAL RESEARCH

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“…The level of expression also correlates with tumour stage, pathological grade and disease specific survival (Dorkin et al, 1999). Furthermore the receptors for FGF8, namely FGFR2IIIc, FGFR3IIIc and FGFR4 are known to be expressed in malignant prostate epithelium (Story et al, 1994;Ittman and Mansukhani, 1997).…”

Section: Introductionmentioning

confidence: 99%

Regulation of FGF8 expression by the androgen receptor in human prostate cancer

et al. 2002

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Fibroblast growth factor 8 (FGF8) has been shown to play a key role in prostate carcinogenesis. It was initially cloned as an androgen induced protein in mouse mammary cancer SC3 cells. In this study, we examined if FGF8 was also regulated by the androgen receptor in human prostate cancer. FGF8b protein expression in resected clinical prostate cancer correlated closely with expression of the androgen receptor (AR). In the androgen sensitive CWR22 prostate xenograft, we observed up-regulation of FGF8b immunoreactivity in testosterone supplemented mice while castration markedly reduced its signal. Furthermore, FGF8b protein expression in AR positive LNCaP cells was similarly enhanced by androgens. The proximal promoter of the human FGF8 gene was cloned into a luciferase reporter construct (FGF8.luc). FGF8.luc activity in AR positive LNCaP and SC3 cells was increased 2.5-fold by androgens. In AR negative DU145 cells, maximal induction of FGF8.luc required both cotransfection of the AR and the presence of androgens. The anti-androgen bicalutamide completely abolished AR mediated FGF8.luc induction. Deletion constructs from FGF8.luc have further defined an active promoter region and an androgen responsive region. Nucleotide analysis of this androgen responsive region has revealed putative androgen response elements. Finally, using ChIP assays we confirmed in vivo interaction between the AR and the androgen responsive region of the FGF8 promoter. Taken together these data provide first evidence that expression of the mitogen FGF8 in prostate cancer is, at least in part, regulated by the androgen receptor at the transcriptional level.

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Characteristics of FGF-receptors Expressed by Stromal and Epithelial Cells Cultured from Normal and Hyperplastic Prostates

Cited by 52 publications

References 39 publications

FGF8 isoform b expression in human prostate cancer

FGF8 isoform b expression in human prostate cancer

Terazosin treatment suppresses basic fibroblast growth factor expression in the rat ventral prostate

Regulation of FGF8 expression by the androgen receptor in human prostate cancer

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