RECEPTORES DE ANDROGENOS Y SU JUEGO EN CÁNCER DE PRÓSTATA

 The androgen receptor plays a suppressive role in epithelial- mesenchymal transition of human prostate cancer stem progenitor cells

Ma Zhifang^*, Wei Liang, Zhang Wei, Hao Bin, Tu Rui, Wu Nan and Zhang Shuhai

• *Corresponding author: Ma Zhifang zhifangma@163.com

Author Affiliations

BMC Biochemistry 2015, 16:13  doi:10.1186/s12858-015-0042-9

Published: 6 May 2015

Abstract (provisional)

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 andγ-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).

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