Oncotarget

Research Papers:

Androgen receptor differentially regulates the proliferation of prostatic epithelial cells in vitro and in vivo

Shu Yang, Ming Jiang, Magdalena M. Grabowska, Jiahe Li, Zachary M. Connelly, Jianghong Zhang, Simon W. Hayward, Justin M. Cates, Guichun Han and Xiuping Yu _

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Oncotarget. 2016; 7:70404-70419. https://doi.org/10.18632/oncotarget.11879

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Abstract

Shu Yang1,*, Ming Jiang2,3,*, Magdalena M. Grabowska4, Jiahe Li1, Zachary M. Connelly1, Jianghong Zhang4, Simon W. Hayward5, Justin M. Cates6, Guichun Han7, Xiuping Yu1

1Department of Biochemistry and Molecular Biology, LSU Health Sciences Center, Shreveport, LA, USA

2Laboratory of Nuclear Receptors and Cancer Research, Center for Basic Medical Research, Nantong University School of Medicine, Nantong, Jiangsu, China

3Institute of Medicine and Public Health, Division of Epidemiology, Department of Medicine, Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN, USA

4Department of Urologic Surgery, Vanderbilt University Medical Center, Nashville, TN, USA

5Department of Surgery, NorthShore University HealthSystem Research Institute, Evanston, IL, USA

6Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN, USA

7Women’s Health Division, Michael E. DeBakey Institute, and Department of Physiology and Pharmacology, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, TX, USA

*These authors have contributed equally to this work

Correspondence to:

Xiuping Yu, email: xyu@lsuhsc.edu

Keywords: prostate, androgen receptor

Received: April 23, 2016    Accepted: August 24, 2016    Published: September 7, 2016

ABSTRACT

Androgens regulate the proliferation and differentiation of prostatic epithelial cells, including prostate cancer (PCa) cells in a context-dependent manner. Androgens and androgen receptor (AR) do not invariably promote cell proliferation; in the normal adult, endogenous stromal and epithelial AR activation maintains differentiation and inhibits organ growth. In the current study, we report that activation of AR differentially regulates the proliferation of human prostate epithelial progenitor cells, NHPrE1, in vitro and in vivo. Inducing AR signaling in NHPrE1 cells suppressed cell proliferation in vitro, concomitant with a reduction in MYC expression. However, ectopic expression of AR in vivo stimulated cell proliferation and induced development of invasive PCa in tissue recombinants consisting of NHPrE1/AR cells and rat urogenital mesenchymal (UGM) cells, engrafted under renal capsule of adult male athymic mice. Expression of MYC increased in the NHPrE1/AR recombinant tissues, in contrast to the reduction seen in vitro. The inhibitory effect of AR signaling on cell proliferation in vitro were reduced by co-culturing NHPrE1/AR epithelial cells with prostatic stromal cells. In conclusion, these studies revealed that AR signaling differentially regulates proliferation of human prostatic epithelia cells in vitro and in vivo through mechanisms involving stromal/epithelial interactions.


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