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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.

Original publication

DOI

10.1054/bjoc.2001.2179

Type

Journal article

Journal

Br J Cancer

Publication Date

14/12/2001

Volume

85

Pages

1928 - 1936

Keywords

Adenocarcinoma, Aged, Aged, 80 and over, Androgens, Biomarkers, Tumor, Disease Progression, Epithelial Cells, Gene Expression Regulation, Neoplastic, Humans, In Situ Hybridization, Male, Middle Aged, Neoplasm Proteins, Neoplasm Staging, Neoplasms, Hormone-Dependent, Nuclear Receptor Coactivator 3, Prostate-Specific Antigen, Prostatic Hyperplasia, Prostatic Neoplasms, RNA, Messenger, RNA, Neoplasm, Receptors, Androgen, Trans-Activators, Transcription Factors, Transcription, Genetic, Transfection, Tumor Cells, Cultured