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Androgen receptor coregulators NOCR1, TIF2, and ARA70 may account for the hydroxyflutamide insensitivity of prostate cancer cells

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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

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Acknowledgments

This project was funded by a Grant from the National Natural Science Fund of China (No. 30901498) and the Natural Science Fund of Shaanxi Province (No. 2009JQ4003). The authors thank Professor Jian-Guang Zhou of the Academy of Military Medical Sciences for her generous donation of the LNCaP cells used for this research.

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Authors and Affiliations

  1. Department of Urology, Tangdu Hospital, Fourth Military Medical University, Xi’an, 710038, Shaanxi, China

    Y. Wang, 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 & T.-Y. Bao

  2. Department of Plastic Surgery, Tangdu Hospital, Fourth Military Medical University, Xi’an, 710038, Shaanxi, China

    J.-Q. Li

  3. Department of Urology, Xijing Hospital, Fourth Military Medical University, Xi’an, 710032, Shaanxi, China

    C. Shao, J.-L. Yuan & Y.-T. Zhang

  4. Department of Experimental Animals, Fourth Military Medical University, Xi’an, 710032, Shaanxi, China

    C.-H. Shi

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  1. Y. Wang
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  2. J.-Q. Li
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  3. C. Shao
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  4. C.-H. Shi
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  5. F. Liu
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  6. Z.-Y. Yang
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  7. J.-X. Qiu
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  8. Y.-M. Li
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  9. Q. Fu
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  10. W. Zhang
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  11. W. Xue
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  12. Y.-H. Lei
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  13. J.-Y. Gao
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  14. J.-Y. Wang
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  15. X.-P. Gao
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  16. J.-L. Yuan
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  17. T.-Y. Bao
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  18. Y.-T. Zhang
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Corresponding authors

Correspondence to J.-L. Yuan, T.-Y. Bao or Y.-T. Zhang.

Additional information

Y. Wang, J.-Q. Li and C. Shao contributed equally to this research.

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Wang, Y., Li, JQ., Shao, C. et al. Androgen receptor coregulators NOCR1, TIF2, and ARA70 may account for the hydroxyflutamide insensitivity of prostate cancer cells. Ir J Med Sci 180, 865–872 (2011). https://doi.org/10.1007/s11845-011-0714-4

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  • DOI: https://doi.org/10.1007/s11845-011-0714-4

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