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Identification and Validation of Novel Androgen-Regulated Genes in Prostate Cancer

Department of Genomics (A.M.V., K.A.G., Y.L., E.L.B.), Wyeth Research, Cambridge, Massachusetts 02140; Department of Oncology (T.M.S., M.A., L.M.G., P.F., Y.Z.), Wyeth Research, Pearl River, New York 10965; and Department of Pathology (W.B.), University of South Florida College of Medicine, Tampa, Florida 33612

Address all correspondence and requests for reprints to: Yixian Zhang, Department of Oncology Research, 401 North Middletown Road, New York, New York 10965. E-mail: zhangy{at}wyeth.com.

Androgen-regulated genes (ARGs) are essential for the development of the prostate. Ironically, ARGs are also responsible for the pathogenesis of prostate cancer. We used oligonucleotide array technology to study the expression profiles of ARGs in LNCaP prostate cancer cells and identified 692 dihydrotestosterone-regulated genes. Representative clusters containing genes with similar expression patterns to prostate-specific antigen and other known ARGs are discussed. Based on functional information, we categorized several candidate targets for prostate cancer therapy and diagnosis. Although many of these candidate targets are known to play an important role in cancer development, several are novel genes to the field of prostate cancer. A cross-comparison study of our results with those that have been previously published from three other array experiments using a similar LNCaP model validated 13 of these candidate targets as androgen-regulated. FKBP51 (FK506-binding immunophilin 51) was found in the same cluster as prostate-specific antigen and its protein expression was increased in LNCaP cells treated with either dihydrotestosterone or synthetic androgen R1881. Results from mining the Gene Logic BioExpress database showed that FKBP51 expression is significantly higher in the prostate cancer group than in the normal and normal adjacent group. Additionally, the androgen-independent prostate tumor xenograft, CWR22R, had higher FKBP51 protein levels than that of the androgen-dependent prostate tumor xenograft, CWR22. A tissue microarray study further revealed that FKBP51 protein expression was higher in prostate cancer specimens than in benign prostate tumor samples. These results suggest the potential value of FKBP51 as a novel diagnostic marker or target for prostate cancer therapy.

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