Relative mRNA expression of prostate-derived E-twenty-six factor and E-twenty-six variant 4 transcription factors, and of uridine phosphorylase-1 and thymidine phosphorylase enzymes, in benign and malignant prostatic tissue

Abstract

Abstract. Prostate cancer is the most frequent urological tumor, and the second most common cancer diagnosed in men. Incidence and mortality are variable and appear to depend on behavioral factors and genetic predisposition. The prostate-derived E-twenty-six factor (PDEF) and E-twenty-six variant 4 (ETV4) transcription factors, and the thymidine phosphorylase (TP) and uridine phosphorylase-1 (UP-1) enzymes, are reported to be components of the pathways leading to tumorigenesis and/or metastasis in a number of tumors. The present study aimed to analyze the mRNA expression levels of these proteins in prostatic cancerous and benign tissue, and their association with clinical and pathological variables. Using quantitative reverse transcription polymerase chain reaction, the mRNA expression levels of PDEF, ETV4, TP and UP-1 were studied in 52 tissue samples (31 of benign prostatic hyperplasia and 21 of prostate adenocarcinomas) obtained from patients treated by transurethral resection of the prostate or by radical prostatectomy. Relative expression was assessed using the ∆-CT method. Data was analyzed using Spearman's tests for correlation. P<0.05 was considered to indicate a statistically significant difference. The results revealed that PDEF, ETV4, UP-1 and TP were expressed in 85.7, 90.5, 95.2 and 100% of the prostate cancer samples, and in 90.3, 96.8, 90.3 and 96.8% of the benign samples, respectively. PDEF and ETV4 exhibited a significantly higher relative expression level in the tumor samples compared with their benign counterparts. The relative expression of TP and UP-1 did not differ significantly between benign and cancerous prostate tissues. The relative expression of TP was moderately and significantly correlated with the expression of ETV4 in the benign tissues. The relative expression of UP-1 was significantly lower in T3 compared with T1 and T2 cancers. These findings indicate that PDEF, ETV4, TP and UP-1 are typically expressed in benign and malignant prostatic tissues. Further studies are necessary to define the role of these proteins as therapeutic targets in prostate cancer.

Heritability and genome-wide association study of benign prostatic hyperplasia (BPH) in the eMERGE network

“…Of the 11 genes included in Table 5, more than half of them have been previously reported such that expression changes have been associated in prostate tissue, often with various stages of prostate cancer. The top result from the GPGE analysis, ETV4 (ETS variant 4) has been previously found in studies of prostate cancer to have significantly higher relative expression in the tumor tissues than in benign samples 79 , as well as an association with poor prognosis 80,81 . We found that increased predicted expression of ETV4 is associated with increased risk of BPH in this study (p-value = 0.0015).…”

E26 transformation-specific variant 4 as a tumor promotor in human cancers through specific molecular mechanisms

“…Clinically, a high level of ETV4 has been found to be associated with Gleason score, pathological tumor stage, and poor prognosis of patients with prostate cancer. 24 Furthermore, ETV4 was found to have a more increased expression in prostate cancer samples than in benign samples, 25 and it was expressed in cell nuclear extracts and cancer tissue protein lysates. 26 However, another group revealed that ETV4 upregulation was rarely found in prostate cancer (3%), and it was particularly more infrequent in higher-grade prostate cancer.…”