Journal article
Androgen Receptor Represses the Neuroendocrine Transdifferentiation Process in Prostate Cancer Cells
Molecular endocrinology (Baltimore, Md.), Vol.17(9), pp.1726-1737
09/01/2003
DOI: 10.1210/me.2003-0031
PMID: 12775765
Abstract
Abstract
Androgen-ablation therapy is an effective method for treating prostate cancer. However, prostate tumors that survive long-term androgen-ablation therapy are classified as androgen-independent as they proliferate in the absence of androgens, and they tend to be enriched for neuroendocrine (NE) cells. Androgen withdrawal causes androgen-dependent prostate cancer cells to adopt a pronounced NE phenotype, suggesting that androgen receptor (AR) represses an intrinsic NE transdifferentiation process in prostate cancer cells. In this report we show that short interfering RNA-induced AR silencing induced a NE phenotype that manifested itself in the growth of dendritic-like processes in both the androgen-dependent LNCaP and androgen-independent LNCaP-AI human prostate cancer cells. Western blot analysis revealed that neuronal-specific enolase, a marker of the neuronal lineage, was increased by AR knockdown in LNCaP cells. The expression levels of the neuronal-specific cytoskeletal proteins β-tubulin III, nestin, and glial acidic fibrillary protein were also characterized in AR knockdown cells. Most interestingly, AR silencing induced β-tubulin III expression in LNCaP cells, while AR knockdown increased glial acidic fibrillary protein levels in both LNCaP and LNCaP-AI cells. Lastly, AR silencing reduced the proliferative capacity of LNCaP and LNCaP-AI cells. Our data demonstrate that AR actively represses an intrinsic NE transdifferentiation process in androgen-responsive prostate cancer cells and suggest a potential link between AR inactivation and the increased frequency of NE cells in androgen-independent tumors.
Details
- Title: Subtitle
- Androgen Receptor Represses the Neuroendocrine Transdifferentiation Process in Prostate Cancer Cells
- Creators
- Michael E Wright - 1Institute for Systems Biology (M.E.W., R.A.), Seattle, Washington 98103Ming-Jer Tsai - 2Department of Molecular and Cellular Biology (M.-J.T.), Baylor College of Medicine, Houston, Texas 77030Ruedi Aebersold - 1Institute for Systems Biology (M.E.W., R.A.), Seattle, Washington 98103
- Resource Type
- Journal article
- Publication Details
- Molecular endocrinology (Baltimore, Md.), Vol.17(9), pp.1726-1737
- Publisher
- Oxford University Press
- DOI
- 10.1210/me.2003-0031
- PMID
- 12775765
- ISSN
- 0888-8809
- eISSN
- 1944-9917
- Language
- English
- Date published
- 09/01/2003
- Academic Unit
- Molecular Physiology and Biophysics
- Record Identifier
- 9984025474802771
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