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http://purl.uniprot.org/citations/32450005http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/32450005http://www.w3.org/2000/01/rdf-schema#comment"

Background

Glutathione peroxidase 3 (Gpx3) protects cells from oxidative stress, and its reduced expression in human prostate cancer has been reported.

Objectives

We hypothesized that Gpx3 might play an important role in the development of prostatic intraepithelial neoplasia (PIN), a pre-cancerous state of the prostate, and aimed to highlight the underlying molecular mechanism.

Materials and methods

The following double-knockout mice Nkx3.1-/-; Gpx3+/+, Nkx3.1-/-; Gpx3+/-, Nkx3.1-/-; Gpx3-/-were produced. Randomly divided animals were weighed, and their genitourinary tract (GUT) weights were determined after euthanasia at 4, 8, and 12 months. The mRNA expression of the genes involved in oxidative stress and Wnt signaling was analyzed in the prostate. Histopathology, ROS, and superoxide dismutase (SOD) activities were also measured.

Results

Loss of Gpx3 did not affect body weight and GUT weight in Nkx3.1 knockout mice. The mRNA expression of SOD3, iNOS, Hmox, and CISD2, which are associated with oxidative stress, was increased in Nkx3.1-/-; Gpx3-/-mice at 4 months but decreased at 8 and 12 months. There was no change in β-catenin and its targets associated with Wnt signaling. Increased ROS and decreased SOD activity were observed in Nkx3.1-/-; Gpx3-/-mice at 12 months of age. The histopathologic score and epithelium thickness were increased, and lumen area was decreased in Gpx3 knockout mice.

Discussion and conclusions

Gpx3 loss increased the hyperplasia of PIN in the pre-cancerous stage of the prostate. Loss of Gpx3 induced oxidative stress. Histopathologically, no invasive carcinoma was identified, and Gpx3 loss did not increase Wnt/β-catenin signaling. Further research on the role of GPX3 in the transition of PIN to invasive carcinoma is needed. We show, for the first time, that the antioxidant enzyme GPX3 plays a vital role in inhibiting hyperplasia in the PIN stage of the prostate gland in vivo."xsd:string
http://purl.uniprot.org/citations/32450005http://purl.org/dc/terms/identifier"doi:10.1111/andr.12828"xsd:string
http://purl.uniprot.org/citations/32450005http://purl.uniprot.org/core/author"Kim U."xsd:string
http://purl.uniprot.org/citations/32450005http://purl.uniprot.org/core/author"Kim J."xsd:string
http://purl.uniprot.org/citations/32450005http://purl.uniprot.org/core/author"Lee J.M."xsd:string
http://purl.uniprot.org/citations/32450005http://purl.uniprot.org/core/author"Park J.H."xsd:string
http://purl.uniprot.org/citations/32450005http://purl.uniprot.org/core/author"Kim C.Y."xsd:string
http://purl.uniprot.org/citations/32450005http://purl.uniprot.org/core/author"Ryu B."xsd:string
http://purl.uniprot.org/citations/32450005http://purl.uniprot.org/core/author"Ahn N."xsd:string
http://purl.uniprot.org/citations/32450005http://purl.uniprot.org/core/author"Bang J."xsd:string
http://purl.uniprot.org/citations/32450005http://purl.uniprot.org/core/date"2020"xsd:gYear
http://purl.uniprot.org/citations/32450005http://purl.uniprot.org/core/name"Andrology"xsd:string
http://purl.uniprot.org/citations/32450005http://purl.uniprot.org/core/pages"1486-1493"xsd:string
http://purl.uniprot.org/citations/32450005http://purl.uniprot.org/core/title"Loss of glutathione peroxidase 3 induces ROS and contributes to prostatic hyperplasia in Nkx3.1 knockout mice."xsd:string
http://purl.uniprot.org/citations/32450005http://purl.uniprot.org/core/volume"8"xsd:string
http://purl.uniprot.org/citations/32450005http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/32450005
http://purl.uniprot.org/citations/32450005http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/32450005
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