Development and characterization of a novel rat model of estrogen-induced mammary cancer.
Development and characterization of a novel rat model of estrogen-induced mammary cancer.
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DOI：
10.1530/erc-14-0539
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发表时间：
2015-04
影响因子：
3.9
通讯作者：
Shull JD
中科院分区：
文献类型：
--
作者：
Dennison KL;Samanas NB;Harenda QE;Hickman MP;Seiler NL;Ding L;Shull JD
17β-雌二醇（E2）诱导乳腺癌的ACI大鼠模型与用于建立乳腺癌病因学的内分泌、遗传和环境基础以及鉴定预防乳腺癌的新型药物和策略高度相关。E2治疗快速诱导雌性ACI大鼠乳腺癌，同时诱导垂体催乳素增生和腺瘤。垂体瘤可导致不期望的发病率，这损害了专注于乳腺癌病因学和预防的长期研究。我们已经确定了E2诱导的乳腺癌和垂体瘤易感性的遗传基础，并利用这些研究中获得的知识开发了一种新的近交系大鼠品系，命名为ACWi，该品系保留了ACI大鼠对E2诱导的乳腺癌的高度易感性，但缺乏与垂体催乳素增生/腺瘤相关的治疗相关发病率。当用E2处理时，雌性ACWi大鼠在116天的中位潜伏期发展出可触及的乳腺癌，到161天的发生率为100%，并且在196天的处理后每只大鼠平均表现出15.6个乳腺肿瘤。这些参数与同期治疗的ACI大鼠观察到的参数无差异。在预期实验终点之前，E2给药的ACWi大鼠均未因除乳腺癌负荷外的任何给药相关发病率而被处以安乐死，而同期给药的ACI大鼠中有20%表现出需要提前处以安乐死的给药相关发病率。ACWi大鼠品系非常适合那些专注于乳腺癌病因学和预防的研究团体使用。
The ACI rat model of 17β-estradiol (E2)-induced mammary cancer is highly relevant for use in establishing the endocrine, genetic and environmental bases of breast cancer etiology and identifying novel agents and strategies for preventing breast cancer. E2 treatment rapidly induces mammary cancer in female ACI rats and simultaneously induces pituitary lactotroph hyperplasia and adenoma. The pituitary tumors can result in undesired morbidity which compromises long term studies focused on mammary cancer etiology and prevention. We have defined the genetic bases of susceptibility to E2-induced mammary cancers and pituitary tumors and have utilized the knowledge gained in these studies to develop a novel inbred rat strain, designated ACWi, that retains the high degree of susceptibility to E2-induced mammary cancer exhibited by ACI rats but lacks the treatment related morbidity associated with pituitary lactotroph hyperplasia/adenoma. When treated with E2, female ACWi rats developed palpable mammary cancer at a median latency of 116 days, an incidence of 100% by 161 days and exhibited an average of 15.6 mammary tumors per rat following 196 days of treatment. These parameters did not differ from that observed for contemporaneously treated ACI rats. None of the E2 treated ACWi rats were euthanized prior to the intended experimental end point due to any treatment related morbidity other than mammary cancer burden, whereas 20% of contemporaneously treated ACI rats exhibited treatment related morbidity that necessitated premature euthanasia. The ACWi rat strain is well suited for use by those in the research community focusing on breast cancer etiology and prevention.