Regulation of TGF-β1 expression by Androgen Deprivation Therapy of prostate cancer
Regulation of TGF-β1 expression by Androgen Deprivation Therapy of prostate cancer
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DOI：
10.1016/j.canlet.2011.08.034
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发表时间：
2012-05-28
期刊：
影响因子：
9.7
通讯作者：
Perlino, Elda
中科院分区：
文献类型：
--
作者：
Fuzio, Paolo;Ditonno, Pasquale;Perlino, Elda
本文研究了体内新辅助雄激素剥夺疗法(ADT)对转化生长因子-β1及其受体T-β-RII表达的影响。雄激素依赖的机制对于理解前列腺癌进展到雄激素非依赖性与疾病死亡率相关至关重要，而转化生长因子-β被认为支持前列腺细胞凋亡，因为其在良性和癌症组织中的表达与雄激素去除相一致。只有在接受新辅助ADT 1个月的患者中首次显示出mRNA和蛋白水平的增加。雄激素消融后，转化生长因子-β表达的短暂增加表明，在前列腺退化过程中，这两条途径是相互配合的。由于没有观察到基因转录活性的变化，这种合作的分子机制可能作用于转录后水平。转化生长因子-β1和T-β-RII特异性信号共同定位于肿瘤前列腺上皮。我们的结果提示，ADT剥夺雄激素1个月后，前列腺癌中的转化生长因子-β1机制发生了改变，提示转化生长因子-β1以自分泌的方式促进前列腺上皮细胞的增殖和抑制细胞的凋亡。(C)2011爱思唯尔爱尔兰有限公司。保留所有权利。
In this paper we studied the in vivo neoadjuvant Androgen Deprivation Therapy (ADT) effect on the expression of TGF-beta 1 and its receptor T beta-RII. Mechanisms of androgen dependence are critical to understanding prostate cancer progression to androgen independence associated with disease mortality, and TGF-beta is thought to support prostatic apoptosis as its expression coincides with androgen ablation in benign and cancer tissues.Increase of both mRNA and protein level were shown for the first time only in the patients who underwent neoadjuvant ADT for 1-month. This transient increase of TGF-beta expression after androgen ablation suggested cooperation of the pathways in prostate regression. Since no alteration was observed in the gene transcriptional activity, the molecular mechanism of this cooperation, probably act at the post-transcriptional level.TGF-beta 1 and T beta-RII specific signals were co-localized within the neoplastic prostate epithelium. our results suggests that the androgens deprivation by means of ADT for 1-month, involves a shift of the TGF-beta 1 mechanism in prostate cancer, suggesting that the TGF-beta 1 promotes prostate epithelial cell proliferation and inhibits apoptosis in a autocrine way. (C) 2011 Elsevier Ireland Ltd. All rights reserved.