Characterization of androgen regulation of ZEB-1 and PSA in 22RVI prostate cancer cells
Characterization of androgen regulation of ZEB-1 and PSA in 22RVI prostate cancer cells
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DOI：
10.1007/978-0-387-69080-3_55
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发表时间：
2008-01-01
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影响因子：
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通讯作者：
Schwendinger, Jamie
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作者：
Anose, Bynthia M.;LaGoo, Lisa;Schwendinger, Jamie
三分之二的转移性前列腺癌（PC）患者在诊断后5年内死亡。具有局部疾病的患者的可比存活率为100%，这清楚地强调了追求和开发生物测定的需要，该生物测定允许预测哪些局部病例最有可能转移。通常测定的前列腺特异性抗原（PSA），虽然被吹捧为转化生物标志物，但最近已被证明在假阳性诊断领域存在问题。然而，它仍然是研究雄激素调节的标志性基因，因为它的表达可靠地受到雄激素如双氢睾酮（DHT）的刺激。在此，我们阐明了氟替卡松（一种确定的抗雄激素）和DHT对PSA和锌指E盒结合因子（ZEB-1）表达的影响。此外，我们测定了两种DHT衍生物对PSA表达的雄激素活性。我们以前的研究已经确定ZEB-1作为前列腺癌转移发生的假定生物标志物。该基因的表达受雄激素调节，并在转移时急剧下降。在目前的研究中，在22 Rv 1（一种雄激素反应性人PC细胞系）中研究了1和10 nM氟替卡松与1和10 nM DHT组合对ZEB-1和PSA表达的影响。此外，在该细胞系中，丙酸睾酮和脱氢异雄酮的影响进行了研究。我们的研究证实了将ZEB-1作为转移性PCa生物标志物的可行性，使用高灵敏度的实时聚合酶链反应（RT-PCR）技术。有趣的是，它还揭示了使用氟替卡松作为治疗性拮抗剂的危险，因为我们在本文中证明了其作为激动剂的惊人能力。
Two-thirds of patients who present with metastatic prostate cancer (PC) are dead within 5 years of diagnosis. The comparable survival rate for patients with localized disease is 100%, which clearly stresses the need for pursuing and developing bioassays that allow prediction of which localized cases are most likely to metastasize. The commonly assayed prostate specific antigen (PSA), while touted as a transformation biomarker, has recently proven to be problematic in the area of false positive diagnoses. It remains, however, a hallmark gene for studying androgen regulation as its expression is reliably stimulated by androgens such as dihydrotestosterone (DHT). Herein, we have elucidated the effects of flutamide (a defined anti-androgen) and DHT on the expression of PSA and Zinc finger E-box Binding factor (ZEB-1). Additionally, we assayed the androgenic capabilities of two DHT derivatives on expression of PSA. Our previous research had identified ZEB-1 as a putative biomarker for the onset of metastasis in prostate cancer. The expression of this gene is regulated by androgen and decreases sharply at metastasis. In the current study, the effects of 1 and 10nM flutamide, in combination with 1 and 10nM DHT, on expression of ZEB-1 and PSA, were investigated in 22Rv1, an androgen-responsive human PC cell line. Also in this cell line, the effects of testosterone propionate and dehydroisoandrosterone were studied. Our research confirmed the feasibility of considering ZEB-1 a metastatic PCa biomarker, using the highly sensitive technique of real-time polymerase chain reaction (RT-PCR). Interestingly, it also revealed the danger of using flutamide as a therapeutic antagonist, as we demonstrate herein its alarming capability to behave as an agonist.