Details

Autor(en) / Beteiligte

• Wang, Y.
• Li, J.-Q.
• Shao, C.
• Shi, C.-H.
• Liu, F.
• Yang, Z.-Y.
• Qiu, J.-X.
• Li, Y.-M.
• Fu, Q.
• Zhang, W.
• Xue, W.
• Lei, Y.-H.
• Gao, J.-Y.
• Wang, J.-Y.
• Gao, X.-P.
• Yuan, J.-L.
• Bao, T.-Y.
• Zhang, Y.-T.

Titel

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

Ist Teil von

• Irish journal of medical science, 2011-12, Vol.180 (4), p.865-872

Ort / Verlag

London: Springer-Verlag

Erscheinungsjahr

2011

Quelle

MEDLINE

Beschreibungen/Notizen

• 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