用于乳腺上皮细胞致癌前瞻性研究的乳腺癌小鼠模型的建立

建立乳腺癌传统模型的方式有两种：(I)将小鼠乳腺癌细胞移植到小鼠体内。(II) 构建基因修饰的小鼠，如p53 KO。第一种方法价格低廉，但由于供体乳腺癌细胞在体外培养过程中会产生大量新抗原，因此不适合用于免疫治疗的研究。第二种方法虽然可以弥补第一种方法的不足。然而，乳腺肿瘤的形成潜伏期超过3个月，不能准备很多具有相似肿瘤大小的小鼠进行治疗实验。本研究的目的是建立在30天内形成多个肿瘤的乳腺癌模型。该方法是连续30天每天向小鼠联合注射雌激素和ATM激酶抑制剂。另一种方法是每天向乳腺上皮P53和BRCA2基因缺失的小鼠注射雌激素。前期数据显示了预期的结果。该项目将揭示雌激素在从正常细胞到癌前阶段，早期癌变，最终发展为乳腺癌这一过程中的作用，同时也为发展免疫治疗提供了可靠的动物模型。

Scientists developed mouse breast cancer (BC) models by (i) transplanting BC cells into mice and (ii) creating gene-modified mice such as p53 KO mice. The first method is inexpensive but is unsuitable for studying immunotherapy because donor BC cells already had large numbers of neoantigens during in vitro culture. The second method can solve this problem. However, the latency period of BC formation is over 3 months, and you could not prepare many mice bearing similar sizes of BCs for therapy experiments. The aim of this study is to establish the BC model that develops multiple BCs in each mouse within 30 days. The method is the consecutive daily injection of estrogens plus ATM kinase inhibitor into mice. Another method is the daily injection of estrogens into mice deficient in both p53 and BRCA2 in mammary epithelium. Preliminary data showed very promising results. The completion of this project will uncover the role of estrogens in very early stages of carcinogenesis from normal cells to the precancer stage and eventually advanced BCs and also provide animal model for developing immunotherapy.