中国癌症杂志2025，Vol.35Issue(8)：769-775,7.DOI:10.19401/j.cnki.1007-3639.2025.08.005
Ptenfl/fl;Trp53fl/fl;Pbsn-iCre+基因编辑小鼠自发形成前列腺癌与乳腺癌的模型构建研究
The research on construction of the spontaneous prostate tumor and breast cancer model of Ptenfl/fl;Trp53fl/fl;Pbsn-iCre+transgenic mouse
摘要
Abstract
Background and purpose:Prostate cancer and breast cancer are highly prevalent malignant tumors,and there occurrence and development are related to the tumor suppressor genes phosphatase and tensin homolog deleted on chremosome ten(Pten)and the transformation related protein 53 gene(Trp53).The loss of function of Trp53 is closely related.The simultaneous loss of the two can accelerate the malignant progression of tumors and induce therapeutic resistance.The gene-edited spontaneous tumor model of mice based on the Cre-loxP system is a key tool for studying the mechanism of cancer.Studies have shown that prostate-specific promoter(probasin,Pbsn)-driven iCre recombinase(Pbsn-iCre)can induce spontaneous prostate cancer in male mice,but its role in female breast cancer and transgender expression characteristics have not yet been clarified.In this study,we constructed Ptenfl/fl;Trp53fl/fl;Pbsn-iCre+transgenic mouse model which was designed to explore its spontaneous tumor phenotype in prostate cancer and breast cancer,and to verify the expression characteristics of Pbsn in breast tissue.Methods:The Ptenfl/fl;Trp53fl/fl;Pbsn-iCre+mouse model was established using Cre-loxP system by hybridization and continuous backcross screening with Ptenfl/fl mouse,Trp53fl/flmouse,and Pbsn-iCre+mouse(Ethical No.:FUSCC-IACUC-2025115).Pten,Trp53 and Pbsn-iCre genotypes were verified by polymerase chain reaction and agarose gel electrophoresis.The incidence of tumor in transgenic mice was monitored,and the histopathological characteristics of tumor were evaluated by hematoxylin-eosin staining.The protein levels of Pten and p53 in prostate and breast tumor tissues were analyzed by immunohistochemistry,and the distributions of Pbsn in breast,prostate,ovary,heart,liver and kidney were detected.Results:Ptenfl/fl;Trp53fl/fl;Pbsn-iCre+male mouse developed spontaneous prostate tumor at age of 5 month,and female mouse developed spontaneous breast tumor at age of 6 months.The pathological manifestations of prostate cancer were invasive acinar adenocarcinoma structure with glandular structure disorder and basement membrane destruction.The pathological manifestations of breast cancer were invasive ductal carcinoma with ductal epithelial dysplasia and interstitial lymphocyte infiltration.Immunohistochemistry confirmed the complete deletion of Pten and p53 proteins in prostate and breast tumor tissues,which verified the prostate and mammary gland specific gene knockout effect.Immunohistochemistry also confirmed that Pbsn protein was specifically expressed in prostate acinar epithelial cells,ovarian tissue,and mammary duct epithelial cells,but not in heart,liver and kidney.Conclusion:Pbsn-iCre is functionally expressed in female mammary glands,and the simultaneous loss of Pten/Trp53 induced by Pbsn-iCre may drive the development of prostate cancer in male and breast cancer in female mouse.关键词
转基因小鼠自发性肿瘤模型/Pbsn-iCre/Pten/Trp53双敲除/前列腺癌/乳腺癌Key words
Transgenic mouse spontaneous tumor model/Pbsn-iCre/Pten/Trp53 double deletion/Prostate cancer/Breast cancer分类
医药卫生引用本文复制引用
吴佳辰,何丽娜,汤鑫茹,唐爽..Ptenfl/fl;Trp53fl/fl;Pbsn-iCre+基因编辑小鼠自发形成前列腺癌与乳腺癌的模型构建研究[J].中国癌症杂志,2025,35(8):769-775,7.基金项目
国家自然科学基金(32270767). National Natural Science Foundation of China(32270767). （32270767）
