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

Abstract

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.

Retracted: Down‐regulation of Jagged‐1 induces cell growth inhibition and S phase arrest in prostate cancer cells

“…6,7 Jagged-1, a Notch receptor ligand, is highly expressed in prostate cancer cells. 8,9 It was found to be increased in the conditioned media in prostate cancer cells. 10 Jagged-1 is significantly over expressed in metastatic prostate cancer as compared with localized prostate cancer or benign prostatic tissues.…”

Direct cancer tissue proteomics: a method to identify candidate cancer biomarkers from formalin-fixed paraffin-embedded archival tissues

“…Furthermore, some proteins that are activated as a consequence of gene activation/inactivation may be used as surrogate biomarkers for early cancer detection (Wilson, 2004;Wright et al, 2005). We have systematically compared the identified protein list from this study with a number of published cDNA microarray data sets (Velasco et al, 2004) and found very little overlap between the regulated mRNAs and identified proteins. These results suggest that more comprehensive characterization of proteomes and mRNAs from normal and cancerous prostates is required for meaningful comparative efforts.…”

Androgen Receptor Promotes the Oncogenic Function of Overexpressed Jagged1 in Prostate Cancer by Enhancing Cyclin B1 Expression via Akt Phosphorylation

“…Expression level of Jag1 has a positive correlation with the progression of prostate cancer Jagged1 and its coding gene, Jag1, were shown, in many studies, to have a closed correlation with prostate cancer (23)(24)(25)(26)(27)(28), which suggests that Jagged1 functions to promote prostate cancer development. Therefore, we further analyzed Jag1 expressions in prostate cancer tissue samples and normal prostate tissue samples to examine whether Jag1 has a significant higher expression level in advanced prostate cancer.…”

“…Jagged1 was found to be highly expressed in most prostate cancer cells and increased in localized prostate cancer compared with benign prostate hyperplasia in the human prostate tumor microarray study (23)(24)(25)(26)(27). Moreover, a positive correlation between Jagged1 and prostate-specific antigen (PSA) recurrence after radical prostatectomy has been found (17), which suggests that high jagged1 protein expression is a strong predictor of prostate cancer recurrence.…”