title: 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.
abstract: 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.
authors.affiliation: Department of Pathology, University of Colorado, Anschutz Medical Campus, 12800 E. 19th Ave., Aurora, CO, 80045, USA.
authors.forename: Jessica L
authors.initials: JL
authors.lastname: Christenson
authors.affiliation: Department of Pathology, University of Colorado, Anschutz Medical Campus, 12800 E. 19th Ave., Aurora, CO, 80045, USA.
authors.forename: Kiel T
authors.initials: KT
authors.lastname: Butterfield
authors.affiliation: Department of Pathology, University of Colorado, Anschutz Medical Campus, 12800 E. 19th Ave., Aurora, CO, 80045, USA.
authors.forename: Nicole S
authors.initials: NS
authors.lastname: Spoelstra
authors.affiliation: Department of Pharmacology and Cancer Biology, Duke University, 450 Research Drive, Durham, NC, 27708, USA.
authors.forename: John D
authors.initials: JD
authors.lastname: Norris
authors.affiliation: Department of Chemistry, Virginia Tech University, 900 West Campus Drive, Blacksburg, VA, 24061, USA.
authors.forename: Jatinder S
authors.initials: JS
authors.lastname: Josan
authors.affiliation: Department of Chemistry, University of Richmond, 28 Westhampton Way, Richmond, VA, 23173, USA.
authors.forename: Julie A
authors.initials: JA
authors.lastname: Pollock
authors.affiliation: Department of Pharmacology and Cancer Biology, Duke University, 450 Research Drive, Durham, NC, 27708, USA.
authors.forename: Donald P
authors.initials: DP
authors.lastname: McDonnell
authors.affiliation: Department of Molecular and Integrative Physiology, University of Illinois, 407 South Goodwin Avenue, Urbana, IL, 61801, USA.
authors.forename: Benita S
authors.initials: BS
authors.lastname: Katzenellenbogen
authors.affiliation: Department of Chemistry, University of Illinois, 600 South Mathews Avenue, Urbana, IL, 61801, USA.
authors.forename: John A
authors.initials: JA
authors.lastname: Katzenellenbogen
authors.affiliation: Department of Pathology, University of Colorado, Anschutz Medical Campus, 12800 E. 19th Ave., Aurora, CO, 80045, USA. jennifer.richer@ucdenver.edu.
authors.forename: Jennifer K
authors.initials: JK
authors.lastname: Richer
mesh_terms: D000726:Androgen Antagonists / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D013196:Dihydrotestosterone / Q000008:administration & dosage / Q000494:pharmacology; D018450:Disease Progression; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D008175:Lung Neoplasms / Q000473:pathology* / Q000556:secondary; D008325:Mammary Neoplasms, Experimental / Q000378:metabolism*; D008324:Mammary Tumor Virus, Mouse / Q000502:physiology; D051379:Mice; D008822:Mice, Transgenic; D011944:Receptors, Androgen / Q000378:metabolism*; D064726:Triple Negative Breast Neoplasms / Q000378:metabolism*
chemical_list: C410798:AR protein, human; C000607144:AR protein, mouse; D000726:Androgen Antagonists; D011944:Receptors, Androgen; D013196:Dihydrotestosterone