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Variable Expression of 5-alpha reductase 2 in Human Prostatic Tissue is Dependent on Methylation in the Epithelial Compartment
Zongwei Wang, Rongbin Ge, Seth Bechis, Shulin Wu, Chin-Lee Wu, Shahin Tabatabaei, Aria Olumi Massachusetts General Hospital, Boston, MA
Introduction: We have found that expression of SRD5A2 is variable and absent in 30% of adult human prostate tissues as a result of methylation of its promoter region. Here we expand our findings to a larger cohort, and further hypothesis that expression of SRD5A2 is variable in the epithelium but consistent in the stroma. Material & Methods: 96 BPH specimens were obtained from patients with symptomatic BPH undergoing TURP surgery. The protein level of SRD5A2 was evaluated by IHC, ELISA and Western blot. Epithelial and stromal compartments were separated by laser capturer microdissection. Statistical analyses were performed with JMP Pro version 11. Results: Similar to our previous findings, we found that 35 of 96 (36.5%) patients did not express the SRD5A2 protein and had methylated CpG promoter regions. The epithelium compartment from hypomethylated tissues had decreased methylation of the SRD5A2 promoter, and high expression of the SRD5A2 protein via ELISA and western blot assay. The epithelium from hypermethylated tissues did not express SRD5A2 protein. However, the expression of SRD5A2 and hypermethylation of the promoter region in the stroma was not variable. Conclusions: Our data suggests that the expression of SRD5A2 is not static and ubiquitous in benign adult prostate tissues. While SRD5A2 can be expressed in both prostate epithelium and stroma, epithelial but not stromal methylation contributes to the variable expression of SRD5A2. Expression of SRD5A2, especially in the epithelium may be used as a gene signature to tailor therapies for more effective treatment of prostatic diseases.
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