Inhibition of androgen-independent growth of prostate cancer xenografts by 17beta-estradiol.
Inhibition of androgen-independent growth of prostate cancer xenografts by 17beta-estradiol.
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发表时间：
2002-04
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通讯作者：
E. Corey;Janna E. Quinn;M. Emond;K. Buhler;L. Brown;R. Vessella
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作者：
E. Corey;Janna E. Quinn;M. Emond;K. Buhler;L. Brown;R. Vessella
雌激素治疗对前列腺癌（CaP）的疗效一直被认为是有益的，但其机制被认为仅仅涉及雄激素水平的降低。然而，新的证据表明，雌激素可能发挥作用的CaP细胞在雄激素的情况下。实验设计将CaP异种移植物（LuCaP 35、LuCaP 49、LuCaP 58、LuCaP 73、PC-3和LNCaP）植入完整的和卵巢切除的雌性小鼠中，以表征在不存在雄激素的情况下的生长和摄取率。卵巢切除的雌性小鼠补充17 β-雌二醇，并测定LuCaP 35 CaP异种移植物摄取率和生长率。逆转录-PCR用于评估CaP异种移植物中雌激素受体信息的存在。结果我们观察到六个CaP异种移植系中的五个在完整的与卵巢切除的雌性动物中的CaP生长的显著抑制。给予切除卵巢的雌性小鼠17 β-雌二醇补充剂导致肿瘤建立的抑制和LuCaP 35生长的减少，与在完整雌性小鼠中观察到的相似。使用逆转录-PCR，我们已经表明，这些异种移植表达雌激素受体β信息。结论：我们已经确定，在动物模型中补充17 β-雌二醇通过不依赖于雄激素作用的机制抑制CaP生长。这就产生了雌激素治疗可能对难治性癌症有潜在用途的可能性。我们在此描述的异种移植模型也可能有助于阐明雌激素对CaP的雄激素非依赖性作用的介导途径。
PURPOSE Estrogen treatment has long been known to be of benefit in prostate cancer (CaP), but its mechanism was thought to involve merely a reduction in androgen levels. However, new evidence indicates that estrogen may exert effects on CaP cells in the absence of androgens. EXPERIMENTAL DESIGN Implantation of CaP xenografts (LuCaP 35, LuCaP 49, LuCaP 58, LuCaP 73, PC-3, and LNCaP) into intact and ovariectomized female mice was done to characterize growth and take rates in the absence of androgens. Ovariectomized female mice were supplemented with 17beta-estradiol, and LuCaP 35 CaP xenograft take and growth rates were determined. Reverse transcription-PCR was used to evaluate the presence of the estrogen receptor messages in CaP xenografts. RESULTS We have observed significant inhibition of CaP growth in intact versus ovariectomized female animals in five of six CaP xenograft lines. 17beta-Estradiol supplements given to ovariectomized female mice led to inhibition of tumor establishment and diminished growth of LuCaP 35 similar to that observed in intact female mice. Using reverse transcription-PCR, we have shown that these xenografts express the estrogen receptor beta message. CONCLUSIONS We have determined that 17beta-estradiol supplementation causes inhibition of CaP growth in an animal model by mechanisms that are independent of androgen action. This gives rise to the possibility that estrogen therapy may be of potential use with hormone-refractory cancers. The xenograft models we describe herein may be useful as well in elucidating the pathways mediating the androgen-independent effects of estrogen on CaP.