title: The androgen receptor plays a suppressive role in epithelial- mesenchymal transition of human prostate cancer stem progenitor cells.
abstract: BACKGROUND
  To investigate the roles of androgen receptor (AR) in epithelial- mesenchymal transition (EMT) in human prostate cancer stem progenitor (S/P) cells isolated from LNCaP cell line.
  
  
  METHODS
  The S/P cells were obtained from LNCaP cell line through florescence-activated cell sorting (FACS). AR was overexpressed in S/P cells through lentivirus. Western blot assay was used to detect the EMT markers expression, such as E Cadherin, N Cadherin, Vimentin and Snail. MTT assay, soft agar colony formation assay, sphere formation assay and migration assay were used to investigate AR's roles in EMT of S/P cells. Cell signaling pathways associated with proliferation and apoptosis of S/P cells were detected simultaneously. And S/P cells were treated with in vitro combinatory use of LY 294002 (inhibitor of AKT signaling molecules) with γ-TT and/or 5-AZA.
  
  
  RESULTS
  Our data showed that S/P cells from LNCaP had high EMT markers expression, more tumorigenesis and strong migration ability. And in S/P cells overexpressed with AR, the expression of EMT markers decreased. In addition, these cells had less proliferation ability, tumorigenesis ability, self-renewal and migration ability. At the same time, targeting S/P cells with AKT signaling pathway inhibitor LY29004 and γ-TT and/or 5-AZA could inhibit S/P cell's proliferation and tumorigenesis.
  
  
  CONCLUSIONS
  Our data suggest that AR played a negative role in EMT of PCa S/P cells, by regulating AKT cell signaling pathway, which could be a new strategy to treat castration resistant prostate cancer (CRPC).
authors.affiliation: Department of Urology, First Hospital of Shanxi Medical University, Taiyuan, 030001, China. zhifangma@163.com.
authors.forename: Ma
authors.initials: M
authors.lastname: Zhifang
authors.affiliation: Department of Urology, First Hospital of Shanxi Medical University, Taiyuan, 030001, China. happy2008con@163.com.
authors.forename: Wei
authors.initials: W
authors.lastname: Liang
authors.affiliation: Department of Urology, First Hospital of Shanxi Medical University, Taiyuan, 030001, China. happy2008con@126.com.
authors.forename: Zhang
authors.initials: Z
authors.lastname: Wei
authors.affiliation: Department of Urology, First Hospital of Shanxi Medical University, Taiyuan, 030001, China. happy2008con@hotmail.com.
authors.forename: Hao
authors.initials: H
authors.lastname: Bin
authors.affiliation: Department of Urology, First Hospital of Shanxi Medical University, Taiyuan, 030001, China. happy2008con@gmail.com.
authors.forename: Tu
authors.initials: T
authors.lastname: Rui
authors.affiliation: Department of Urology, First Hospital of Shanxi Medical University, Taiyuan, 030001, China. happy2008con@yahoo.com.
authors.forename: Wu
authors.initials: W
authors.lastname: Nan
authors.affiliation: Department of Urology, First Hospital of Shanxi Medical University, Taiyuan, 030001, China. happy2008con@aliyun.com.
authors.forename: Zhang
authors.initials: Z
authors.lastname: Shuhai
mesh_terms: D001374:Azacitidine / Q000031:analogs & derivatives / Q000494:pharmacology; D045744:Cell Line, Tumor; D000066673:Cell Self Renewal / Q000187:drug effects; D002839:Chromans / Q000494:pharmacology; D002867:Chromones / Q000494:pharmacology; D000077209:Decitabine; D004357:Drug Synergism; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects; D006801:Humans; D008297:Male; D009025:Morpholines / Q000494:pharmacology; D014411:Neoplastic Stem Cells / Q000187:drug effects / Q000473:pathology*; D011471:Prostatic Neoplasms / Q000473:pathology*; D011944:Receptors, Androgen / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D014810:Vitamin E / Q000031:analogs & derivatives / Q000494:pharmacology
chemical_list: C410798:AR protein, human; D002839:Chromans; D002867:Chromones; D009025:Morpholines; D011944:Receptors, Androgen; D014810:Vitamin E; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; C013649:plastochromanol 8; D000077209:Decitabine; D001374:Azacitidine