Stable suppression of tumorigenicity by Pin1-targeted RNA interference in prostate cancer
Stable suppression of tumorigenicity by Pin1-targeted RNA interference in prostate cancer
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DOI：
10.1158/1078-0432.ccr-05-0457
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发表时间：
2005-10-15
影响因子：
11.5
通讯作者：
Aoki, I
中科院分区：
文献类型：
--
作者：
Ryo, A;Uemura, H;Aoki, I
目的：肽基脯氨酰异构酶Pin1在包括前列腺癌在内的实体癌的肿瘤发生中起催化作用。在本研究中，我们试图确定潜在的Pin1靶向基因沉默在抑制细胞生长和致瘤性在前列腺癌。实验设计：逆转录病毒介导的RNA干扰靶向Pin1在PC 3和LNCaP细胞中表达，细胞生长和几个转化特性进行了研究。结果如下：Pin1特异性小干扰RNA构建体在PC3和LNCaP细胞中的稳定表达显著降低了细胞增殖、集落形成、迁移和侵袭，但强烈增强了由血清耗竭或用抗癌剂治疗诱导的凋亡反应。此外，Pin1耗尽显着抑制肿瘤发生的潜力在无胸腺小鼠，导致抑制肿瘤生长和angiogeneisisis.Conclusions：这些结果强烈表明，Pin1起着重要的作用，不仅在肿瘤发生，但也在前列腺癌细胞的转化表型的维护。因此，Pin1可能作为一个有前途的治疗靶点，特别是对复发性前列腺肿瘤。
Purpose: The peptidyl-prolyl isomrase Pin1 plays a catalytic role in oncogenesis in solid cancers, including prostate cancer. In the present study, we sought to determine the potential of Pin1-targeted gene silencing in inhibiting cellular growth and tumorigenicity in prostate cancer.Experimental Design: A retrovirus-mediated RNA interference targeting Pin1 was expressed in PC3 and LNCaP cells, and cell growth and several transformed properties were investigated. Results: The stable expression of Pin1-specific small interfering RNA constructs in PC3 and LNCaP cells significantly reduced cellular proliferation, colony formation, migration, and invasion but strongly enhanced the apoptotic response induced by serum depletion or treatment with anticancer agents. Furthermore, Pin1 depletion significantly suppressed tumorigenic potential in athymic mice, resulting in the inhibition of both tumor growth and angiogeneisis.Conclusions: These results strongly suggest that Pin1 plays an important role not only in tumorigenesis but also in the maintenance of the transformed phenotype in prostate cancer cells. Hence, Pin1 may serve as a promising therapeutic target, particularly for recurrent prostate tumors.