A model of spontaneous mouse mammary tumor for human estrogen receptor- and progesterone receptor-negative breast cancer

Abstract

Breast cancer (BC) is the most frequently malignancy in women. Therefore, establishment of an animal model for the development of preventative measures and effective treatment for tumors is required. A novel heterogeneous spontaneous mammary tumor animal model of Kunming mice was generated. The purpose of this study was to characterize the spontaneous mammary tumor model. Histopathologically, invasive nodular masses of pleomorphic tubular neoplastic epithelial cells invaded fibro-vascular stroma, adjacent dermis and muscle tissue. Metastatic spread through blood vessel into liver and lungs was observed by hematoxylin eosin staining. No estrogen receptor (ER) or progesterone receptor (PR) immunoreactivity was detected in their associated malignant tumors, human epidermal growth factor receptor-2 (HER-2) protein weak expression was found by immunohistochemistry. High expression of vascular endothelial growth factor (VEGF), moderate or high expression of c-Myc and cyclin D1 were observed in tumor sections at different stages (2, 4, 6 and 8 weeks after cancer being found) when compared with that of the normal mammary glands. The result showed that the model is of an invasive ductal carcinoma. Remarkably in the mouse model, ER and PR-negative and HER2 weak positivity are observed. The high or moderate expressions of breast cancer markers (VEGF, c-Myc and cyclin D1) in mammary cancer tissue change at different stages. To our knowledge, this is the first report of a spontaneous mammary model displaying colony-strain, outbred mice. This model will be an attractive tool to understand the biology of anti-hormonal breast cancer in women.

Animal models for exploring the pharmacokinetics of breast cancer therapies

“…Kunming mice are the largest number of closed colony mice in production in China which spontaneously form estrogen receptor negative, progesterone receptor negative, and HER2 expressing mammary tumors [27]. These mice have been shown to produce tumors that are weakly expressing the HER2 protein by immunohistochemistry, but have a high vascular endothelial growth factor, c-Myc and cyclin D1 [27].…”

“…These mice have been shown to produce tumors that are weakly expressing the HER2 protein by immunohistochemistry, but have a high vascular endothelial growth factor, c-Myc and cyclin D1 [27]. While these tumors do metastasize to distant organs such as the liver and lung, they do so hematogenously rather than via the lymphatic system, which is in stark contrast to human breast cancer progression [27].…”

“…These mice have been shown to produce tumors that are weakly expressing the HER2 protein by immunohistochemistry, but have a high vascular endothelial growth factor, c-Myc and cyclin D1 [27]. While these tumors do metastasize to distant organs such as the liver and lung, they do so hematogenously rather than via the lymphatic system, which is in stark contrast to human breast cancer progression [27]. There have been efforts to utilize such spontaneous models as well as transgenic HER2 models to test novel therapeutics for chemoprevention in breast cancer; however, the authors concede that the dramatic differences between these models and human breast cancer greatly limit the applicability of their results outside of clinical trials [28].…”

Pristimerin overcomes adriamycin resistance in breast cancer cells through suppressing Akt signaling

“…Breast cancer is the most frequently diagnosed cancer and the leading cause of cancer-associated mortality among females (1,2), accounting for 23% of the total cancer cases and 14% of cancer mortalities (3). Chemotherapy serves an important role in the treatment of breast cancer.…”

Oestrogen receptor negativity in breast cancer: a cause or consequence?

“…The mammary tumours are either ER- or PR-negative, whereas Her-2 protein is weakly positive. In addition, these tumours also had high expression of VEGF, moderate or high expression of c-Myc and cyclin D1 that elucidates that this is one of the first spontaneous mammary models displaying colony strain of outbred mice and could serve as a pivotal tool in understanding the biology of anti-hormonal breast cancer in women [59]. These mouse models can be further explored to study the origin of ER negativity and to further understand the endocrine resistance.…”