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Expression of Tip60, an androgen receptor coactivator, and its role in prostate cancer development

Lookup NU author(s): Vincent Gnanapragasam, Dr Piyush Mehta, Dr Ian Logan, Mark Brady, Susan Cook, Professor Hing Leung, Professor David Neal, Professor Craig Robson

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Abstract

Prostate cancer (CaP) is initially androgen sensitive and responsive to hormone ablation therapy. However, cancer growth recurs despite androgen deprivation in the majority of cases of advanced disease. The molecular basis of this progression still remains unknown. The significance of androgen receptor (AR) coactivator proteins in this androgen-dependent malignancy is only beginning to emerge. In the present study, we examined the role of Tat interactive protein, 60kDa (Tip60), an AR coactivator, in CaP progression. In hormone refractory CaP biopsies, we observed a nuclear accumulation of Tip60 expression in contrast to a more diffuse distribution pattern observed in benign prostate hyperplasia and primary CaP. Furthermore, in both the prostate xenograft model CWR22 and the LNCaP CaP cell line, we observed that androgen withdrawal promoted upregulation of Tip60 as well as nuclear accumulation. In contrast, androgen exposure resulted in decreased Tip60 expression that was more closely linked to a cytoplasmic presence. Chromatin immunoprecipitation analysis revealed Tip60's recruitment to the PSA gene promoter in both androgen-dependent and -independent cell lines. Thus, in vitro and in vivo data support a possible role for Tip60 in the molecular pathway leading to the development of androgen-independent CaP following long-term androgen deprivation therapy.


Publication metadata

Author(s): Halkidou, K., Gnanapragasam, V. J., Mehta, P. B., Logan, I. R., Brady, M. E., Cook, S., Leung, H. Y., Neal, D. E., Robson, C. N.

Publication type: Article

Publication status: Published

Journal: Oncogene

Year: 2003

Volume: 22

Issue: 16

Pages: 2466-2477

Print publication date: 24/04/2003

ISSN (print): 0950-9232

ISSN (electronic): 1476-5594

URL: http://dx.doi.org.10.1038/sj.onc.1206342

DOI: 10.1038/sj.onc.1206342

PubMed id: 12717424


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