Expression of RAC 3, a steroid hormone receptor co-activator in prostate cancer

Gnanapragasam, V., Leung, H. , Pulimood, A., Neal, D. and Robson, C. (2001) Expression of RAC 3, a steroid hormone receptor co-activator in prostate cancer. British Journal of Cancer, 85(12), pp. 1928-1936. (doi: 10.1054/bjoc.2001.2179)

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RAC 3, one of the p160 family of co-activators is known to enhance the transcriptional activity of a number of steroid receptors. As co-activators are also known to enhance androgen receptor (AR) activity, we investigated the role of RAC 3 in the context of prostate cancer. In prostate cancer cell lines, we found variable levels of the RAC 3 protein with highest expression seen in AR-positive LNCaP cells, moderate expression in AR-negative PC 3 cells and low-level expression in AR-negative DU 145 cells. Immuno-precipitation studies showed that endogenous RAC 3 interacted with the AR in vivo and transfection assays confirmed that RAC 3 enhanced AR transcriptional activity. In clinical prostate tissue, we found strong RAC 3 mRNA expression and immuno-histochemistry demonstrated that in benign tissue, the protein was expressed predominantly in luminal cells, while in primary malignant epithelium it was more homogeneously expressed. In a series of 37 patients, the levels of RAC 3 expression correlated significantly with tumour grade (P = 0.01) and stage of disease (P = 0.03) but not with serum PSA levels. In addition moderate or high RAC 3 expression was associated with poorer disease-specific survival (P = 0.03). We conclude that RAC 3 is an important co-activator of the AR in the prostate and may have an important role in the progression of prostate cancer.

Item Type:Articles
Glasgow Author(s) Enlighten ID:Leung, Professor Hing
Authors: Gnanapragasam, V., Leung, H., Pulimood, A., Neal, D., and Robson, C.
College/School:College of Medical Veterinary and Life Sciences > School of Cancer Sciences
Journal Name:British Journal of Cancer

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