Watson Philip A, Ellwood-Yen Katharine, King Jennifer C, Wongvipat John, Lebeau Michelle M, Sawyers Charles L
Division of Hematology/Oncology, Department of Medicine, University of California at Los Angeles, 90095, USA.
Cancer Res. 2005 Dec 15;65(24):11565-71. doi: 10.1158/0008-5472.CAN-05-3441.
Insights into the molecular basis of hormone-refractory prostate cancer have principally relied on human prostate cancer cell lines, all of which were derived from patients who had already failed hormonal therapy. Recent progress in developing genetically engineered mouse prostate cancer models provides an opportunity to isolate novel cell lines from animals never exposed to hormone ablation, avoiding any potential bias conferred by the selective pressure of the castrate environment. Here we report the isolation of such a cell line (Myc-CaP) from a c-myc transgenic mouse with prostate cancer. Myc-CaP cells have an amplified androgen receptor gene despite no prior exposure to androgen withdrawal and they retain androgen-dependent transgene expression as well as androgen-dependent growth in soft agar and in mice. Reexpression of c-Myc from a hormone-independent promoter rescues growth in androgen-depleted agar but not in castrated mice, showing a clear distinction between the molecular requirements for hormone-refractory growth in vitro versus in vivo. Myc-CaP cells represent a unique reagent for dissecting discreet steps in hormone-refractory prostate cancer progression and show the general utility of using genetically engineered mouse models for establishing new prostate cancer cell lines.
对激素难治性前列腺癌分子基础的深入了解主要依赖于人类前列腺癌细胞系，所有这些细胞系均来自已接受激素治疗但失败的患者。在开发基因工程小鼠前列腺癌模型方面的最新进展提供了一个机会，可从从未接受过激素去除的动物中分离出新的细胞系，避免去势环境的选择压力所带来的任何潜在偏差。在此，我们报告了从一只患有前列腺癌的c-myc转基因小鼠中分离出这样一种细胞系（Myc-CaP）。尽管Myc-CaP细胞此前未接触过雄激素剥夺，但它们的雄激素受体基因却发生了扩增，并且在软琼脂中和小鼠体内仍保留雄激素依赖性转基因表达以及雄激素依赖性生长。从一个不依赖激素的启动子重新表达c-Myc可挽救雄激素缺乏的琼脂中的生长，但在去势小鼠中则不能，这表明在体外与体内激素难治性生长的分子需求之间存在明显差异。Myc-CaP细胞是剖析激素难治性前列腺癌进展中离散步骤的独特试剂，并显示了使用基因工程小鼠模型建立新的前列腺癌细胞系的普遍实用性。
