The androgen receptor plays a suppressive role in epithelial- mesenchymal transition of human prostate cancer stem progenitor cells.
BMC Biochem
; 16: 13, 2015 May 06.
Article
em En
| MEDLINE
| ID: mdl-25943311
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).
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Neoplasias da Próstata
/
Células-Tronco Neoplásicas
/
Receptores Androgênicos
/
Transição Epitelial-Mesenquimal
Limite:
Humans
/
Male
Idioma:
En
Ano de publicação:
2015
Tipo de documento:
Article