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转化生长因子β对人前列腺基质细胞表型的调节作用

Modulation of phenotype of human prostatic stromal cells by transforming growth factor-betas.

作者信息

Hisataki Toshihiro, Itoh Naoki, Suzuki Kazuhiro, Takahashi Atsushi, Masumori Naoya, Tohse Noritsugu, Ohmori Yuki, Yamada Shizuo, Tsukamoto Taiji

机构信息

Department of Urology, Sapporo Medical University, Sapporo, Japan.

出版信息

Prostate. 2004 Feb 1;58(2):174-82. doi: 10.1002/pros.10320.

Abstract

BACKGROUND

We investigated the effects of transforming growth factor (TGF)-betas on morphological and receptor phenotypes, as well as proliferation of four currently established human prostatic myofibroblast cell lines and one commercially available prostatic stromal cell line.

METHODS

The effects of TGF-betas on morphological changes and proliferation of the cells were studied by immunohistochemistry and bromodeoxyuridine assay, respectively. The expression of alpha 1-receptor subtypes was measured by real time quantitative reverse transcription-polymerase chain reaction (RT-PCR) and the radioligand binding assay for the receptors was also performed.

RESULTS

TGF-betas 1, 2, and 3 induced expression of desmin and myosin of cells of the established cell lines, and significantly inhibited their growth. The alpha 1a-receptor was expressed only in the commercially available cell line and alpha 1b and 1d, in all cell lines. TGF-beta 1 suppressed the expression of all three subtypes of the alpha 1-receptor. The binding sites of cells of all the cell lines were reduced by treatment with this growth factor.

CONCLUSIONS

TGF-betas may induce human prostatic stromal cells to express the smooth muscle phenotype and inhibited their growth. However, the growth factor reduced the binding sites of the receptor and suppressed mRNA expression of its subtypes, suggesting that morphological and receptor phenotypes may be regulated via more than one pathway by TGF-beta(s).

摘要

背景

我们研究了转化生长因子(TGF)-β对四种目前已建立的人前列腺肌成纤维细胞系和一种市售前列腺基质细胞系的形态和受体表型以及增殖的影响。

方法

分别通过免疫组织化学和溴脱氧尿苷测定法研究TGF-β对细胞形态变化和增殖的影响。通过实时定量逆转录-聚合酶链反应(RT-PCR)测量α1-受体亚型的表达,并进行受体的放射性配体结合测定。

结果

TGF-β1、2和3诱导已建立细胞系的细胞中结蛋白和肌球蛋白的表达,并显著抑制其生长。α1a-受体仅在市售细胞系中表达,而α1b和1d在所有细胞系中表达。TGF-β1抑制α1-受体所有三种亚型的表达。用这种生长因子处理后,所有细胞系细胞的结合位点均减少。

结论

TGF-β可能诱导人前列腺基质细胞表达平滑肌表型并抑制其生长。然而,生长因子减少了受体的结合位点并抑制了其亚型的mRNA表达,这表明形态和受体表型可能通过不止一条途径由TGF-β调节。

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