Transforming growth factor-beta promotes invasion in tumorigenic but not in nontumorigenic human prostatic epithelial cells.
Transforming growth factor-beta promotes invasion in tumorigenic but not in nontumorigenic human prostatic epithelial cells.
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发表时间：
2006
期刊：
影响因子：
11.2
通讯作者：
Mingfang Ao;K. Williams;N. Bhowmick;S. Hayward
中科院分区：
文献类型：
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作者：
Mingfang Ao;K. Williams;N. Bhowmick;S. Hayward
转化生长因子- β (tgf - β)是一种多效性生长因子，其作用取决于环境，包括剂量、靶细胞类型和环境。tgf - β可以引发促进生长和抑制生长的活性。在正常组织中，tgf - β通常起到限制生长和维持分化的作用。然而，在肿瘤发生过程中，tgf - β表达和细胞反应的变化可促进肿瘤的发生。本研究探讨了tgf - β对非致瘤性人前列腺上皮细胞系BPH1和三种衍生致瘤亚系BPH1(CAFTD)1、BPH1(CAFTD)3和BPH1(CAFTD)5的影响。数据显示tgf - β对非致瘤性和致瘤性细胞有不同的作用。非致瘤性细胞被tgf -抑制生长。相反，致瘤亚群不受生长抑制，而是在tgf - β的作用下经历上皮到间充质转化（EMT）。致瘤细胞系显示出组成性的磷酸化Akt水平升高，这通过阻断Smad3和p21核易位来调节它们对tgf - β的反应。在tgf - β刺激的致瘤亚系中，活化的Akt使细胞逃脱细胞周期阻滞。磷脂酰肌醇3-激酶/Akt通路也参与tgf - β诱导的EMT，这里通过诱导vimentin表达和增强细胞运动性来定义。在体内，具有组成性tgf - β信号活性的致瘤细胞显示EMT的侵袭性增加，EMT表达特异性位于肿瘤侵袭前部的vimentin。这些数据表明，恶性转化后tgf - β可以在促进前列腺癌中发挥直接作用，并且这些反应在体内是特定环境的。
Transforming growth factor-beta (TGF-beta) is a pleiotropic growth factor with actions that are dependent on circumstances, including dose, target cell type, and context. TGF-beta can elicit both growth-promoting and growth-suppressive activities. In normal tissues, TGF-beta generally acts to restrict growth and maintain differentiation. However, during tumorigenesis, changes in TGF-beta expression and cellular responses can promote tumorigenesis. The present study examines the effects of TGF-beta on the nontumorigenic human prostatic epithelial cell line BPH1 and on three derivative tumorigenic sublines BPH1(CAFTD)1, BPH1(CAFTD)3, and BPH1(CAFTD)5. The data show that TGF-beta has different effects on the nontumorigenic and tumorigenic cells. The nontumorigenic cells are growth inhibited by TGF-beta. In contrast, the tumorigenic sublines are not growth inhibited but instead undergo an epithelial to mesenchymal transformation (EMT) in response to TGF-beta. The tumorigenic lines show constitutively elevated levels of phosphorylated Akt, which modulates their response to TGF-beta by blocking Smad3 and p21 nuclear translocation. On TGF-beta stimulation of the tumorigenic sublines, the activated Akt allows the cell to escape cell cycle arrest. The phosphatidylinositol 3-kinase/Akt pathway is also involved in TGF-beta-induced EMT, defined here by induction of vimentin expression and enhanced cellular motility. In vivo, tumorigenic cells with constitutively active TGF-beta signaling show increased invasion with EMT, which express vimentin, located specifically at the invasive front of the tumor. These data indicate that following malignant transformation TGF-beta can play a direct role in promoting prostatic cancer and further that these responses are context specific in vivo.