BCRT：异质的雌激素阳性乳腺癌模型可进行更精确的药物检测

细胞的培养是均一的，然而人类的肿瘤却不是这样。近日来自美国科罗拉多大学癌症中心的研究者报道了，人体雌激素阳性（ER+）乳腺癌模型可以保留其异质性，允许科学家更精确地运用测试药物来检测疾病。相关研究成果刊登在了近日的国际杂志<em>Breast Cancer Research and Treatment</em>上。

“乳腺癌从来没有黑白之分，这些模型允许我们将其中的灰色部分挑选出来”，研究者Peter这样说，他的意思是并不是所有的人体雌激素阳性乳腺癌细胞都是雌激素阳性的。相反在人类肿瘤细胞中，它们或许是依赖雌激素生存的细胞，而且对于抗雌激素疗法比较敏感。在同质ER+细胞培养液中检测测试药物或许几乎不能预测药物是如何对异质肿瘤细胞进行作用的。

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这种异质性所引发的乳腺癌大部分具有致命性的特征-有抗雌激素药物的能力。理论上来说，医生可以用抗雌激素药物来杀灭ER+细胞，但是这并不能减缓其他类型乳腺癌细胞的生长，这些乳腺癌细胞或许将来会变成主要的癌症细胞类型，这些ER-细胞更趋向于很难杀灭。

这种新型的异质乳腺癌细胞模型为研究者们带来了两件事情，第一，研究者可以更精确地检测药物的有效性；第二，相比寻找常见乳腺癌的特征，维持这些肿瘤的异质性使得研究者研究什么对于肿瘤是唯一的。

近日的研究中，经过外科手术所得到的人类乳腺肿瘤样品被移植进入动物模型中，肿瘤同样可以维持其异质性。研究者Kabos表示，下一步的治疗方法将帮助我们理解在肿瘤中ER+和ER-的比例，并且帮助我们解密其调节机制。

编译自：<a title="" href="http://medicalxpress.com/news/2012-08-heterogeneous-er-breast-cancer-accurate.html" target="_blank">Heterogeneous ER breast cancer models allow more accurate drug testing</a>
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<img src="http://www.bioon.com/biology/UploadFiles/201208/2012080700022152.jpg" alt="" width="113" height="149" border="0" />

<a title="" href="http://dx.doi.org/doi:10.1007/s10549-012-2164-8" target="_blank">doi:10.1007/s10549-012-2164-8</a>
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<br/><strong>Patient-derived luminal breast cancer xenografts retain hormone receptor heterogeneity and help define unique estrogen-dependent gene signatures</strong><br/>


Peter Kabos, Jessica Finlay-Schultz, Chunling Li, Enos Kline, Christina Finlayson, Joshua Wisell, Christopher A. Manuel, Susan M. Edgerton, J. Chuck Harrell and Anthony Elias, et al.

Bypassing estrogen receptor (ER) signaling during development of endocrine resistance remains the most common cause of disease progression and mortality in breast cancer patients. To date, the majority of molecular research on ER action in breast cancer has occurred in cell line models derived from late stage disease. Here we describe patient-derived ER+ luminal breast tumor models for the study of intratumoral hormone and receptor action. Human breast tumor samples obtained from patients post surgery were immediately transplanted into NOD/SCID or NOD/SCID/ILIIrg−/− mice under estrogen supplementation. Five transplantable patient-derived ER+ breast cancer xenografts were established, derived from both primary and metastatic cases. These were assessed for estrogen dependency, steroid receptor expression, cancer stem cell content, and endocrine therapy response. Gene expression patterns were determined in select tumors ±estrogen and ±endocrine therapy. Xenografts morphologically resembled the patient tumors of origin, and expressed similar levels of ER (5–99 %), and progesterone and androgen receptors, over multiple passages. Four of the tumor xenografts were estrogen dependent, and tamoxifen or estrogen withdrawal (EWD) treatment abrogated estrogen-dependent growth and/or tumor morphology. Analysis of the ER transcriptome in select tumors revealed notable differences in ER mechanism of action, and downstream activated signaling networks, in addition to identifying a small set of common estrogen-regulated genes. Treatment of a naïve tumor with tamoxifen or EWD showed similar phenotypic responses, but relatively few similarities in estrogen-dependent transcription, and affected signaling pathways. Several core estrogen centric genes were shared with traditional cell line models. However, novel tumor-specific estrogen-regulated potential target genes, such as cancer/testis antigen 45, were uncovered. These results evoke the importance of mapping both conserved and tumor-unique ER programs in breast cancers. Furthermore, they underscore the importance of primary xenografts for improved understanding of ER+ breast cancer heterogeneity and development of personalized therapies.

<br/>来源：生物谷

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