Wang Qingfei, Ding Hui, Wang Hai, Li Ping, Liu Baorui, Zhang Kui
Department of Laboratory Medicine, Nanjing Drum Tower Hospital, School of Medicine, Nanjing University, Nanjing, Jiangsu 210008, P.R. China.
The Comprehensive Cancer Center and Department of Oncology, Nanjing Drum Tower Hospital, School of Medicine, Nanjing University, Nanjing, Jiangsu 210008, P.R. China.
Oncol Rep. 2015 Jan;33(1):179-84. doi: 10.3892/or.2014.3574. Epub 2014 Oct 30.
Breast cancer cell lines and mouse models are valuable tools for investigating the biology of and developing potential therapeutics for human breast carcinoma. The PTEN-/-/NIC mouse is a genetically engineered mouse model for ErbB2/Neu-overexpressing/‑PTEN deficient breast carcinoma with histopathological and molecular features relevant to the luminal subtype of primary human breast cancer. However, the PTEN-/-/NIC model develops multifocal and aggressive mammary tumors with a short life-span, which greatly impedes its preclinical usage. To complement the genetic engineering approach and to facilitate the future application of this model, in the present study, two newly established cell lines, NICP20 and NICP21, from PTEN-/-/NIC mammary tumors are described. These NICP20 and NICP21 cells retained the crucial molecular phenotype similar to the origin, as confirmed by genotyping and western blot analysis. These cells induced tumors in immunocompetent syngeneic mice by mammary fat pad injection and produced lung metastasis when injected intravenously. Tumors induced by these cells displayed luminal‑like histologic morphology and hyperactivation of Akt which are similar to PTEN-/-/NIC tumors. Immunohistochemical staining also revealed that tumors induced by the NICP20 and NICP21 cells showed a high proliferative level, comparable angiogenesis and T-cell infiltration properties similar to PTEN-/-/NIC tumors. Therefore, these NICP20 and NICP21 cells represent an alternative and useful model system to enhance our understanding of the nature of ErbB2-positive breast cancers, particularly accompanying PTEN loss and to facilitate further experimental therapeutic studies.
乳腺癌细胞系和小鼠模型是研究人类乳腺癌生物学特性及开发潜在治疗方法的宝贵工具。PTEN-/-/NIC小鼠是一种基因工程小鼠模型，用于研究ErbB2/Neu过表达/PTEN缺陷型乳腺癌，其具有与原发性人类乳腺癌管腔亚型相关的组织病理学和分子特征。然而，PTEN-/-/NIC模型会发展出多灶性侵袭性乳腺肿瘤，且寿命较短，这极大地阻碍了其在临床前的应用。为了补充基因工程方法并促进该模型的未来应用，在本研究中，描述了两种新建立的来自PTEN-/-/NIC乳腺肿瘤的细胞系NICP20和NICP21。通过基因分型和蛋白质免疫印迹分析证实，这些NICP20和NICP21细胞保留了与起源相似的关键分子表型。通过乳腺脂肪垫注射，这些细胞在具有免疫活性的同基因小鼠中诱导肿瘤形成，静脉注射时会发生肺转移。这些细胞诱导的肿瘤表现出类似管腔的组织形态学和Akt的过度激活，这与PTEN-/-/NIC肿瘤相似。免疫组织化学染色还显示，NICP20和NICP21细胞诱导的肿瘤显示出高增殖水平、与PTEN-/-/NIC肿瘤相当的血管生成和T细胞浸润特性。因此，这些NICP20和NICP21细胞代表了一种替代且有用的模型系统，可增强我们对ErbB2阳性乳腺癌本质的理解，特别是伴随PTEN缺失的情况，并有助于进一步的实验性治疗研究。
