Regulation of prostate-specific antigen by activin A in prostate cancer LNCaP cells
Regulation of prostate-specific antigen by activin A in prostate cancer LNCaP cells
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DOI：
10.1152/ajpendo.00443.2003
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发表时间：
2004-06-01
影响因子：
5.1
通讯作者：
Kihara, K
中科院分区：
文献类型：
--
作者：
Fujii, Y;Kawakami, S;Kihara, K
激活素是一种多功能生长和分化因子，通过垂体促性腺激素刺激FSH- β基因表达和FSH分泌。卵泡抑素结合激活素，导致激活素生物活性的中和。激活素/卵泡抑素系统存在于前列腺组织中。前列腺特异性抗原（PSA）在男性生殖生理中起着重要的作用，也是前列腺癌的重要肿瘤标志物。因此，PSA的调控具有重要的临床意义。先前的研究表明，PSA主要受雄激素的调节。在本研究中，我们评估了激活素A对表达功能性激活素受体和雄激素受体以及PSA的前列腺癌LNCaP细胞增殖和PSA生成的直接影响。LNCaP细胞用激活素A和5 -二氢睾酮（DHT）联合或不联合其拮抗剂（卵泡抑素或非甾体抗雄激素比卡鲁胺）处理。激活素A以剂量依赖的方式抑制LNCaP细胞的生长，而DHT则以双相方式促进LNCaP细胞的生长。与激活素A和DHT对细胞生长的相反作用相反，激活素A和DHT都上调了LNCaP细胞的PSA基因表达，增加了PSA的分泌。激活素A和二氢睾酮增加PSA的作用是协同的或相加的。卵泡抑素或比卡鲁胺对细胞生长或PSA生成无影响。激活素A对LNCaP细胞的作用被卵泡抑素阻断，而不是被比卡鲁他胺阻断，而DHT的作用被比卡鲁他胺阻断，而不是被卵泡抑素阻断。激活素A上调PSA的产生，其作用是通过雄激素受体不依赖的途径。激活素/卵泡抑素系统可能是前列腺组织中PSA基因转录和分泌的生理调节剂，激活素可能与雄激素协同上调体内PSA。
Activins are multifunctional growth and differentiation factors and stimulate FSH-beta gene expression and FSH secretion by the pituitary gonadotropes. Follistatins bind activin, resulting in the neutralization of activin bioactivity. The activin/follistatin system is present in the prostate tissue. Prostate-specific antigen (PSA) plays an important role in male reproductive physiology as well as being very important as a tumor marker for prostate cancer. Thus the regulation of PSA has important clinical implications. Previous studies showed that PSA is primarily regulated by androgens. In the present study, we evaluated the direct effects of activin A on the proliferation and PSA production of prostate cancer LNCaP cells, which express functional activin receptors and androgen receptor and PSA. LNCaP cells were treated with activin A and 5alpha-dihydrotestosterone (DHT) with or without their antagonists ( follistatin or the nonsteroidal anti-androgen bicalutamide). Activin A decreased cell growth of LNCaP cells in a dose-dependent manner, whereas DHT increased it in a biphasic manner. In contrast to their opposing actions on cell growth, both activin A and DHT upregulated PSA gene expression and increased PSA secretion by LNCaP cells. The effects of activin A and DHT to increase PSA production were synergistic or additive. Follistatin or bicalutamide was without effect on cell growth or PSA production. The effects of activin A on LNCaP cells were blocked by follistatin, not by bicalutamide, whereas effects of DHT were prevented by bicalutamide, not by follistatin. Activin A upregulates PSA production, and the effect is through an androgen receptor-independent pathway. The activin/follistatin system can be a physiological modulator of PSA gene transcription and secretion in the prostate tissue, and activins may cooperate with androgen to upregulate PSA in vivo.