Erschienen in:
01.12.2011 | Original Article
Androgen receptor coregulators NOCR1, TIF2, and ARA70 may account for the hydroxyflutamide insensitivity of prostate cancer cells
verfasst von:
Y. Wang, J.-Q. Li, C. Shao, C.-H. Shi, F. Liu, Z.-Y. Yang, J.-X. Qiu, Y.-M. Li, Q. Fu, W. Zhang, W. Xue, Y.-H. Lei, J.-Y. Gao, J.-Y. Wang, X.-P. Gao, J.-L. Yuan, T.-Y. Bao, Y.-T. Zhang
Erschienen in:
Irish Journal of Medical Science (1971 -)
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Ausgabe 4/2011
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Abstract
Introduction
Prostate cancer cells can switch from an androgen-dependent state to an androgen-independent state after a continuous androgen ablation therapy. However, the molecular mechanisms underlying this switch are still unclear. Therefore, we explored the change in androgen receptor (AR)-related gene expression during this transition in a novel cell model.
Material and methods
Prostate cancer cells were continuously treated with competitive androgen receptor inhibitor hydroxyflutamide for 1.5 years, which yielded an flutamide-insensitive LNCaP subline, LNCaP-flu, as confirmed by MTT assays, flow cytometry, and electron microscopy. We analyzed the differences in gene expression in LNCaP-flu cells and LNCaP cells using gene chips and follow-up RT-PCR.
Results
Over 2,428 genes were differentially expressed between these cell lines: 1,194 were down-regulated and 1,234 were up-regulated. Three genes in particular were considered related to the androgen-dependent transition: NCOR1, TIF2 (NCOA2), and ARA70 (NCOA4). There were no apparent changes in expression of the androgen receptor or prostate-specific antigen.
Conclusion
ARs and associated coregulators play a central role in the flutamide-insensitive transition of prostate cancer cells. Although AR expression does not change during this transition, the change in AR coregulators may be a critical factor in the development of antiandrogen insensitivity