MMTV-PyMT and Derived Met-1 Mouse Mammary Tumor Cells as Models for Studying the Role of the Androgen Receptor in Triple-Negative Breast Cancer Progression

• Published in: Hormones & cancer Vol. 8; no. 2; pp. 69 - 77
• Main Authors: Christenson, Jessica L., Butterfield, Kiel T., Spoelstra, Nicole S., Norris, John D., Josan, Jatinder S., Pollock, Julie A., McDonnell, Donald P., Katzenellenbogen, Benita S., Katzenellenbogen, John A., Richer, Jennifer K.
• Format: Journal Article
• Language: English
• Published: New York Springer US 01-04-2017
• Subjects: Androgen Antagonists - administration & dosage; Androgen Antagonists - pharmacology; Animals; Cell Biology; Cell Line, Tumor; Cell Nucleus - metabolism; Cell Proliferation - drug effects; Dihydrotestosterone - administration & dosage; Dihydrotestosterone - pharmacology; Disease Progression; Endocrinology; Female; Gene Expression Regulation, Neoplastic - drug effects; Humans; Internal Medicine; Lung Neoplasms - pathology; Lung Neoplasms - secondary; Mammary Neoplasms, Experimental - metabolism; Mammary Tumor Virus, Mouse - physiology; Medicine; Medicine & Public Health; Mice; Mice, Transgenic; Microbiology; Oncology; Original Article; Receptors, Androgen - metabolism; Systems Biology; Triple Negative Breast Neoplasms - metabolism; Androgen Receptor; Enzalutamide; Androgen Receptor Expression; TNBC Cell; Breast Cancer
• ISSN: 1868-8497; 1868-8500
• DOI: 10.1007/s12672-017-0285-6

Triple-negative breast cancer (TNBC) has a faster rate of metastasis compared to other breast cancer subtypes, and no effective targeted therapies are currently FDA-approved. Recent data indicate that the androgen receptor (AR) promotes tumor survival and may serve as a potential therapeutic target in TNBC. Studies of AR in disease progression and the systemic effects of anti-androgens have been hindered by the lack of an AR-positive (AR+) immunocompetent preclinical model. In this study, we identified the transgenic MMTV-PyMT (mouse mammary tumor virus-polyoma middle tumor-antigen) mouse mammary gland carcinoma model of breast cancer and Met-1 cells derived from this model as tools to study the role of AR in breast cancer progression. AR protein expression was examined in late-stage primary tumors and lung metastases from MMTV-PyMT mice as well as in Met-1 cells by immunohistochemistry (IHC). Sensitivity of Met-1 cells to the AR agonist dihydrotestosterone (DHT) and anti-androgen therapy was examined using cell viability, migration/invasion, and anchorage-independent growth assays. Late-stage primary tumors and lung metastases from MMTV-PyMT mice and Met-1 cells expressed abundant nuclear AR protein, while negative for estrogen and progesterone receptors. Met-1 sensitivity to DHT and AR antagonists demonstrated a reliance on AR for survival, and AR antagonists inhibited invasion and anchorage-independent growth. These data suggest that the MMTV-PyMT model and Met-1 cells may serve as valuable tools for mechanistic studies of the role of AR in disease progression and how anti-androgens affect the tumor microenvironment.