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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.
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.
Afiliación
  • Christenson JL; Department of Pathology, University of Colorado, Anschutz Medical Campus, 12800 E. 19th Ave., Aurora, CO, 80045, USA.
  • Butterfield KT; Department of Pathology, University of Colorado, Anschutz Medical Campus, 12800 E. 19th Ave., Aurora, CO, 80045, USA.
  • Spoelstra NS; Department of Pathology, University of Colorado, Anschutz Medical Campus, 12800 E. 19th Ave., Aurora, CO, 80045, USA.
  • Norris JD; Department of Pharmacology and Cancer Biology, Duke University, 450 Research Drive, Durham, NC, 27708, USA.
  • Josan JS; Department of Chemistry, Virginia Tech University, 900 West Campus Drive, Blacksburg, VA, 24061, USA.
  • Pollock JA; Department of Chemistry, University of Richmond, 28 Westhampton Way, Richmond, VA, 23173, USA.
  • McDonnell DP; Department of Pharmacology and Cancer Biology, Duke University, 450 Research Drive, Durham, NC, 27708, USA.
  • Katzenellenbogen BS; Department of Molecular and Integrative Physiology, University of Illinois, 407 South Goodwin Avenue, Urbana, IL, 61801, USA.
  • Katzenellenbogen JA; Department of Chemistry, University of Illinois, 600 South Mathews Avenue, Urbana, IL, 61801, USA.
  • Richer JK; Department of Pathology, University of Colorado, Anschutz Medical Campus, 12800 E. 19th Ave., Aurora, CO, 80045, USA. jennifer.richer@ucdenver.edu.
Horm Cancer ; 8(2): 69-77, 2017 04.
Article en En | MEDLINE | ID: mdl-28194662
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.
Asunto(s)

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Receptores Androgénicos / Neoplasias de la Mama Triple Negativas / Neoplasias Pulmonares / Neoplasias Mamarias Experimentales Límite: Animals / Female / Humans Idioma: En Revista: Horm Cancer Año: 2017 Tipo del documento: Article País de afiliación: Estados Unidos

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Receptores Androgénicos / Neoplasias de la Mama Triple Negativas / Neoplasias Pulmonares / Neoplasias Mamarias Experimentales Límite: Animals / Female / Humans Idioma: En Revista: Horm Cancer Año: 2017 Tipo del documento: Article País de afiliación: Estados Unidos