Prostate, 2013, 73(16):1747–1760.

Genistein versus ICI 182, 780: An Ally or Enemy in Metastatic Progression of Prostate Cancer

Hisae Nakamura, Yuwei Wang, Hui Xue, et al

Experimental Therapeutics, BC Cancer Agency, Vancouver, British Columbia, Canada; Terry Fox Laboratory, BC Cancer Agency, Vancouver, British Columbia, Canada; The Vancouver Prostate Centre, Vancouver, British Columbia, Canada; et al

BACKGROUND:

Androgen signalling through the androgen receptor (AR) plays a critical role in prostate cancer (PCa) initiation and progression. Estrogen in synergy with androgen is essential for cell growth of the normal and malignant prostate. However, the exact role that estrogen and the estrogen receptor play in prostate carcinogenesis remains unclear. We have previously demonstrated the metastasis-promoting effect of an estrogen receptor beta (ERβ) agonist (genistein) in a patient-derived PCa xenograft model mimicking localized and metastatic disease.

METHODS:

To test the hypothesis that the tumor-promoting activity of genistein was due to its estrogenic properties, we treated the xenograft-bearing mice with genistein and an anti-estrogen compound (ICI 182, 780) and compared the differential gene expression using microarrays.

RESULTS:

Using a second xenograft model which was derived from another patient, we showed that genistein promoted disease progression in vivo and ICI 182, 780 inhibited metastatic spread. The microarray analysis revealed that the metallothionein (MT) gene family was differentially expressed in tumors treated by these compounds. Using qRT-PCR, the differences in expression levels were validated in the metastatic and non-metastatic LTL313 PCa xenograft tumor lines, both of which were originally derived from the same PCa patient.

CONCLUSIONS:

Together our data provide evidence that genistein stimulates and ICI 182, 780 inhibits metastatic progression, suggesting that these effects may be mediated by ERβ signalling.

美国《前列腺》，2013年12月

金雀异黄素与 ICI 182,780: 在前列腺癌转移性进展中的朋友或者敌人

中村寿惠，王玉伟，薛辉，等

加拿大哥伦比亚BC癌症机构实验治疗学；泰瑞  福克斯实验室；温哥华前列腺中心等

背景︰

雄激素信号通过雄激素受体 (AR) 在前列腺癌 (PCa) 的启动和进展中发挥重要作用。雌激素与雄激素的协同作用对正常和恶性前列腺细胞的生长至关重要。然而，雌激素和雌激素受体在前列腺癌中的确切作用尚不清楚。我们先前的实验表明雌激素受体β（ERβ） 激动剂（金雀异黄素）在模仿局部和转移的异种移植PCa病人中的转移促进的作用。

方法︰

为了测试这一假设，金雀异黄素的肿瘤促进活性是由于其雌激素特性，我们用金雀异黄素和抗雌激素化合物 (ICI 182，780)治疗裸鼠移植瘤荷瘤小鼠并且使用微阵列比较基因的差异性表达。

结果︰

使用源于另一位病人的第二种异种移植模型，我们发现金雀异黄素促进了体内的疾病进展而 ICI 182，780 则抑制了转移蔓延。微阵列分析揭示了金属硫蛋白 (MT) 基因家族在用这些化合物治疗的肿瘤中被差异性表达。使用 qRT-PCR在最初源自同一 PCa 病人的转移性和非转移性 LTL313 PCa 异种移植肿瘤中，验证了表达水平的差异。

结论︰

综合我们的数据证明金雀异黄素刺激而 ICI 182 780抑制了转移的进程，表明这些影响可能有ERβ 信号调节。