Androgen-independent LNCaP cells are a subline of LNCaP cells with a more aggressive phenotype and androgen suppresses their growth by inducing cell cycle arrest at the G1 phase

Yu,Pan; Duan,Xiuzhi; Cheng,Yue; Liu,Chunhua; Chen,Yuhua; Liu,Weiwei; Yin,Binbin; Wang,Xuchu; Tao,Zhihua

doi:10.3892/ijmm.2017.3125

Androgen-independent LNCaP cells are a subline of LNCaP cells with a more aggressive phenotype and androgen suppresses their growth by inducing cell cycle arrest at the G1 phase

Authors:
- Pan Yu
- Xiuzhi Duan
- Yue Cheng
- Chunhua Liu
- Yuhua Chen
- Weiwei Liu
- Binbin Yin
- Xuchu Wang
- Zhihua Tao
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Affiliations: Department of Laboratory Medicine, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang 310009, P.R. China
Published online on: September 7, 2017 https://doi.org/10.3892/ijmm.2017.3125
Pages: 1426-1434
Copyright: © Yu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Androgen deprivation therapy (ADT, surgical or chemical castration) is the mainstay treatment for metastatic prostate cancer (PCa); however, patients ineluctably relapse despite extremely low androgen levels. This evolution of PCa indicates its lethal progression. In this study, to mimic the traits of clinical PCa progression in vitro, we investigated the alterations in the cell biological characteristics in androgen-independent LNCaP cells (LNCaP-AI cells) compared with LNCaP cells. We also examined the effects of androgen on LNCaP and LNCaP-AI cell proliferation, androgen receptor (AR) expression and prostate-specific antigen (PSA) secretion. Furthermore, AR was silenced in the LNCaP and LNCaP-AI cells to detect the roles taht AR plays in cell growth, apoptosis and PSA secretion. We found that prolonged androgen ablation increased the LNCaP-AI cell growth rate and cell invasiveness, and induced epithelial-mesenchymal transition in the LNCaP-AI cells. Moreover, despite the fact that the LNCaP and LNCaP-AI cells expressed equal amounts of AR protein, androgen induced a greater secretion of PSA in the LNCaP-AI cells than in the LNCaP cells. The proliferation of the LNCaP-AI cells was not dependent on, but was suppressed by androgen, which led to arrest at the G1 phase. Conversely, androgen significantly increased LNCaP cell proliferation by promoting the G1-S transition. Moreover, the silencing of AR suppressed LNCaP and LNCaP-AI cell growth by inducing cell cycle arrest at the G1 phase rather than promoting apoptosis, and reduced PSA secretion. On the whole, our data suggest that LNCaP-AI cells have a more more aggressive phenotype compared with the LNCaP cells; AR remains a critical factor in the LNCaP-AI cells, and androgen suppresses LNCaP-AI cell growth by blocking the cell cycle at the G1 phase.

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