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Stromal SRD5A2 promotes prostate growth through WNT5A-LEF1-IGF1 signaling in benign prostatic hyperplasia

ABSTRACT: Stromal SRD5A2 promotes prostate growth through WNT5A-LEF1-IGF1 signaling in benign prostatic hyperplasia

PROVIDER: PRJNA1299475 | ENA |

REPOSITORIES: ENA

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Stromal SRD5A2 promotes prostate growth through WNT5A-LEF1-IGF1 signaling in benign prostatic hyperplasia

Project description:Steroid 5 alpha-reductase type 2 (SRD5A2) is a key enzyme in androgen metabolism and a pharmacologic target in benign prostatic hyperplasia (BPH). While SRD5A2 is known to mediate stromal-epithelial interactions that influence prostate growth, the relationship between baseline SRD5A2 expression and prostate volume remains unclear. In this study, we analyzed SRD5A2 expression in human prostate tissues from the Medical Therapy of Prostatic Symptoms (MTOPS) trial and institutional biorepository cohorts. Quantitative assessments were performed and correlations were evaluated between expression level of SRD5A2, WNT5A, prostate volume, and tissue signaling profiles. SRD5A2 expression was significantly associated with total prostate and transition zone volume. Stromal-specific WNT5A expression showed a strong positive correlation with SRD5A2, while neither serum nor tissue dihydrotestosterone levels correlated with SRD5A2 expression. In Srd5a2-null mice, Wnt5a expression in the prostate stroma was dependent on Srd5a2 and showed region-specific regulation. Mechanistically, SRD5A2 overexpression in human prostate stromal cells upregulated WNT5A and Lymphoid Enhancer-Binding Factor 1 (LEF1), activated insulin-like growth factor 1 (IGF1) signaling, increased proliferation, and reduced apoptosis. Conditioned media from these cells enhanced epithelial proliferation through paracrine IGF1 activity. This study provides the first evidence that SRD5A2 promotes prostate growth through a stromal WNT5A-LEF1-IGF1 paracrine signaling axis independent of androgen levels, suggesting a novel therapeutic mechanism relevant for BPH patients with resistance to conventional 5 alpha-reductase inhibitor therapy.

2025-08-05 | GSE304244 | GEO

Genomic Analysis of Benign Prostatic Hyperplasia

Project description:Genomic Analysis of Benign Prostatic Hyperplasia

| PRJNA492375 | ENA

Genomic Analysis of Benign Prostatic Hyperplasia

Project description:Genomic Analysis of Benign Prostatic Hyperplasia

| PRJNA492376 | ENA

Genome-wide analysis of prostatic tissue gene expression from patients with benign prostatic hyperplasia

Project description:Analysis of gene expression in prostatic tissue from BPH patients with and without SRD5A2 gene methylation. The hypothesis is that BPH patients with DNA methylation of the SRD5A2 gene promoter have impaired conversion of testosterone to dihydrotestosterone, and therefore may use an alternative signaling pathway for prostatic tissue growth. Here, we compare gene expression profiles of SRD5A2-methylated vs. unmethylated prostatic tissue to nominate alternative biological pathways relevant in each molecular subtype of BPH.

2017-10-01 | GSE101486 | GEO

Expression data from benign prostatic hyperplasia samples and normal controls

Project description:To further development of our gene expression signature for benign prostatic hyperplasia, we conducted expression profiles of BPH and normal samples.

2020-05-28 | GSE119195 | GEO

Different expressed genes in epithelium and stromal of Benign Prostatic Hyperplasia

2011-08-10 | GSE31323 | GEO

Copy number analysis of BPH (Benign Prostatic Hyperplasia)

Project description:Copy number analysis of BPH (Benign Prostatic Hyperplasia)

| PRJNA510968 | ENA

Different expressed genes in epithelium and stromal of Benign Prostatic Hyperplasia

Project description:To identify the genes differently expressed in the epithelium and the stromal of Benign Prostatic Hyperplasia (BPH), we collect the epithelium and the stromal from the patients with benign prostatic hyperplasia by laser micro-dissection. And then, Affymetrix HG-U133_Plus_2 gene-chip was used to detect and compare the expression level of genes. To find which genes are most abundantly expressed in epithelium and stromal and what is the role of these genes in the pathogenesis of BPH. 8 prostate tissues were collected from patients undergone transurethral resection of the prostate (TURP) with informed consent. Each tissue was embedded in O.C.T and subsequently used for laser micro-dissection. The total RNA was isolated from each sample and equally mixed for gene-chip assay.

2011-08-09 | E-GEOD-31323 | biostudies-arrayexpress

Spatial transcriptomic profiles of prostate tissue obtained from a patient diagnosed with benign prostatic hyperplasia (BPH).

Project description:ST profiles reveals the alterations in epithelial cells in Benign Prostatic Hyperplasia.

2024-05-01 | GSE242249 | GEO

Comparative serum proteome profiling of canine benign prostatic hyperplasia before and after castration

Project description:Benign prostatic hyperplasia (BPH) is the most prevalent prostatic condition in older intact dogs; nonetheless, clinical diagnosis and management remain inconsistent. This study employed in-solution digestion coupled with nano-liquid chromatography-tandem mass spectrometry (nanoLC-MS/MS) to assess serum proteome profiling of dogs with BPH and those dogs after castration.

2024-10-11 | PXD046059 | JPOST Repository

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