The Differential Effects of Anti-Diabetic Thiazolidinedione on Prostate Cancer Progression Are Linked to the TR4 Nuclear Receptor Expression Status.
The Differential Effects of Anti-Diabetic Thiazolidinedione on Prostate Cancer Progression Are Linked to the TR4 Nuclear Receptor Expression Status.
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抗糖尿病噻唑烷二酮对前列腺癌进展的不同作用与 TR4 核受体表达状态有关。
DOI：
10.1016/j.neo.2015.02.005
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发表时间：
2015-04
期刊：
影响因子：
4.8
通讯作者：
Chang, Chawnshang
中科院分区：
文献类型：
--
作者：
Lin, Shin-Jen;Lin, Chang-Yi;Yang, Dong-Rong;Izumi, Kouji;Yan, Emily;Niu, Xiaodan;Chang, Hong-Chiang;Miyamoto, Hiroshi;Wang, Nancy;Li, Gonghui;Chang, Chawnshang
胰岛素增敏剂噻唑烷二酮类 (TZD) 自从发现其能够通过过氧化物酶体增殖物激活受体 (PPAR) 的反式激活来改变胰岛素抵抗以来，一直被用作抗糖尿病药物。然而，它们对肝炎、心血管疾病和膀胱癌的副作用导致在美国和欧洲的销售受到一些限制。在这里，我们发现 TZD 对前列腺癌 (PCa) 进展的潜在影响可能与 TR4 核受体表达有关。临床调查发现，9%的前列腺癌患者肿瘤中有一个等位基因TR4缺失。当 TR4 被敲低时，TZD 会增加 PCa 细胞的细胞生长和侵袭。相比之下，TZD 降低了野生型 TR4 的 PCa 细胞的 PCa 进展。机制剖析发现，TZD 处理 TR4 敲低的 CWR22Rv1 和 C4-2 细胞后，哈维大鼠肉瘤 (HRAS) 癌基因增加，而 HRAS 抑制剂的中断导致 TZD 诱导的 PCa 进展逆转。总之，这些结果表明，TZD 治疗可能会促进 PCa 进展，具体取决于可能与临床相关的 TR4 表达状态，因为对于接受 TZD 治疗且有一个等位基因 TR4 缺失的糖尿病 PCa 患者可能需要格外小心。
The insulin sensitizers, thiazolidinediones (TZDs), have been used as anti-diabetic drugs since the discovery of their ability to alter insulin resistance through transactivation of peroxisome proliferator-activated receptors (PPARs). However, their side effects in hepatitis, cardiovascular diseases, and bladder cancer resulted in some selling restrictions in the USA and Europe. Here, we found that the potential impact of TZDs on the prostate cancer (PCa) progression might be linked to the TR4 nuclear receptor expression. Clinical surveys found that 9% of PCa patients had one allele TR4 deletion in their tumors. TZD increased cell growth and invasion in PCa cells when TR4 was knocked down. In contrast, TZD decreased PCa progression in PCa cells with wild type TR4. Mechanism dissection found that the Harvey Rat Sarcoma (HRAS) oncogene increased on TZD treatment of the TR4 knocked-down CWR22Rv1 and C4-2 cells, and interruption with HRAS inhibitor resulted in reversal of TZD-induced PCa progression. Together, these results suggest that TZD treatment may promote PCa progression depending on the TR4 expression status that may be clinically relevant since extra caution may be needed for those diabetic PCa patients receiving TZD treatment who have one allele TR4 deletion.
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影响因子：
2.9
作者：
Bolden A;Bernard L;Jones D;Akinyeke T;Stewart LV
通讯作者：
Stewart LV
影响因子：
3.3
作者：
Izumi, Koji;Li, Yi;Miyamoto, Hiroshi
通讯作者：
Miyamoto, Hiroshi
影响因子：
158.5
作者：
Nissen, Steven E.;Wolski, Kathy
通讯作者：
Wolski, Kathy
影响因子：
2.9
作者：
Lu, Chien-Jung;Sun, Yu;Hsu, Chung Y.
通讯作者：
Hsu, Chung Y.
DOI：
10.1073/pnas.91.13.6040
发表时间：
1994-06-21
影响因子：
11.1
作者：
CHANG, CS;DASILVA, SL;BURBACH, JPH
通讯作者：
BURBACH, JPH