谱系示踪技术在乳腺上皮增殖、转化及肿瘤转移过程中应用

The Application of Lineage Tracing Technique in Mammary Epithelial Proliferation,Transformation and Tumor Metastasis

乳腺上皮细胞在哺乳动物中起合成和分泌乳汁的功能,同时介导乳腺肿瘤的发生,但乳腺癌转移过程存在很大争议。研究利用遗传谱系示踪技术追踪乳腺上皮细胞,示踪其增殖、转化形成乳腺肿瘤细胞,并迁移形成肺转移灶的过程。利用小鼠为实验模型,采用KitCreER转基因小鼠与报告基因小鼠R26-Ai47结合靶向示踪乳腺上皮细胞,然后结合乳腺原位肿瘤小鼠模型MMTV-PyMT形成3基因型,观察在青春期和老年期小鼠乳腺肿瘤细胞向肺转移的情况。结果:KitCreER可特异性标记乳腺管腔上皮细胞,可发生增殖转化贡献形成乳腺肿瘤细胞,肿瘤细胞在青春期不发生肺转移灶但在老年期会形成明显的肺转移灶。从分子遗传学角度解析乳腺上皮细胞在乳腺癌中的作用特点。

Mammary epithelial cells play the functions of synthesizing and secreting milk in mammals,and mediating the occurrence of breast tumors,but the process of breast cancer metastasis is very controversial.Therefore,this study used genetic lineage tracing technology to trace mammary epithelial cells to trace their proliferation,transformation to form mammary tumor cells,and migration to form lung metastases.Method:Using mice as an experimental model,the combination of Kit CreER transgenic mice and reporter gene mouse R26-Ai47 was used to target and trace mammary epithelial cells.Then combined with the mammary orthotopic tumor mouse model MMTV-PyMT to form three genotypes,we observed the metastasis of mammary tumor cells to the lungs in adolescent and old mice.Results:Kit CreER can specifically label mammary luminal epithelial cells,and can proliferate and transform to contribute to the formation of mammary tumor cells.Tumor cells do not develop lung metastases in adolescence but develop significant lung metastases in old age.Significance:The role of mammary epithelial cells in breast cancer was analyzed from the perspective of molecular genetics,and new ideas were provided for the study of antitumor drug therapeutic targets in human breast cancer.