The pluripotency factor Nanog is directly upregulated by the Androgen Receptor in prostate cancer cells. Issue 15 (31st August 2014)

• Record Type: Journal Article
• Authors: Kregel, Steven; Szmulewitz, Russell Z.; Griend, Donald J. Vander
• Is Part Of: Prostate. Volume 74:Issue 15(2014)
• Page Start: 1530
• Page End: 1543
• Publication Date: 2014-08-31
• Subjects: Prostate -- Diseases -- Periodicals; 616
• DOI: 10.1002/pros.22870
• Languages: English
• ISSNs: 0270-4137

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <sec id="pros22870-sec-0001" sec-type="section"> <title>BACKGROUND</title> <p>The Androgen Receptor (AR) is a nuclear hormone receptor that functions as a critical oncogene in all stages of prostate cancer progression, including progression to castration‐resistance following androgen‐deprivation therapy. Thus, identifying and targeting critical AR‐regulated genes is one potential method to block castration‐resistant cancer proliferation. Of particular importance are transcription factors that regulate stem cell pluripotency; many of these genes are emerging as critical oncogenes in numerous tumor cell types. Of these, Nanog has been previously shown to increase the self‐renewal and stem‐like properties of prostate cancer cells. Thus, we hypothesized that Nanog is a candidate AR target gene that may impart castration‐resistance.</p> </sec> <sec id="pros22870-sec-0002" sec-type="section"> <title>METHODS</title> <p>We modulated AR signaling in LNCaP prostate cancer cells and assayed for Nanog expression. Direct AR binding to the <italic>NANOG</italic> promoter was tested using AR Chromatin Immunoprecipation (ChIP) and analyses of publically available AR ChIP‐sequencing data‐sets. Nanog over‐expressing cells were analyzed for cell growth and cytotoxicity in response to the AR antagonist enzalutamide and the microtubule stabilizing agent docetaxel.</p> </sec> <sec id="pros22870-sec-0003" sec-type="section"> <title>RESULTS</title> <p>AR signaling upregulates Nanog mRNA and protein. AR binds directly to the <italic>NANOG</italic> promoter, and was not identified within 75 kb of the <italic>NANOGP8</italic> pseudogene, suggesting the <italic>NANOG</italic> gene locus was preferentially activated. Nanog overexpression in LNCaP cells increases overall growth, but does not increase resistance to enzalutamide or docetaxel.</p> </sec> <sec id="pros22870-sec-0004" sec-type="section"> <title>CONCLUSIONS</title> <p>Nanog is a novel oncogenic AR target gene in prostate cancer cells, and stable expression of Nanog increases proliferation and growth of prostate cancer cells, but not resistance to enzalutamide or docetaxel. <italic>Prostate 74:1530–1543, 2014</italic>. © 2014 Wiley Periodicals, Inc.</p> </sec> </abstract>