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Prostate cancer ris...
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Srinivasan, SrilakshmiQueensland University of Technology
(författare)
Prostate cancer risk-associated single-nucleotide polymorphism affects prostate-specific antigen glycosylation and its function
- Artikel/kapitelEngelska2019
Förlag, utgivningsår, omfång ...
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2019-01-01
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Oxford University Press (OUP),2019
Nummerbeteckningar
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LIBRIS-ID:oai:lup.lub.lu.se:fe87050f-7dea-4b49-98f2-d878f3ace6f2
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https://lup.lub.lu.se/record/fe87050f-7dea-4b49-98f2-d878f3ace6f2URI
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https://doi.org/10.1373/clinchem.2018.295790DOI
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Språk:engelska
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Sammanfattning på:engelska
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Ämneskategori:art swepub-publicationtype
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Ämneskategori:ref swepub-contenttype
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BACKGROUND: Genetic association studies have reported single-nucleotide polymorphisms (SNPs) at chromosome 19q13.3 to be associated with prostate cancer (PCa) risk. Recently, the rs61752561 SNP (Asp84Asn substitution) in exon 3 of the kallikrein-related peptidase 3 (KLK3) gene encoding prostate-specific antigen (PSA) was reported to be strongly associated with PCa risk (P 2.3 108). However, the biological contribution of the rs61752561 SNP to PCa risk has not been elucidated. METHODS: Recombinant PSA protein variants were generated to assess the SNP-mediated biochemical changes by stability and substrate activity assays. PC3 cell–PSA overexpression models were established to evaluate the effect of the SNP on PCa pathogenesis. Genotype-specific correlation of the SNP with total PSA (tPSA) concentrations and free/total (F/T) PSA ratio were determined from serum samples. RESULTS: Functional analysis showed that the rs61752561 SNP affects PSA stability and structural conformation and creates an extra glycosylation site. This PSA variant had reduced enzymatic activity and the ability to stimulate proliferation and migration of PCa cells. Interestingly, the minor allele is associated with lower tPSA concentrations and high F/T PSA ratio in serum samples, indicating that the amino acid substitution may affect PSA immunoreactivity to the antibodies used in the clinical immunoassays. CONCLUSIONS: The rs61752561 SNP appears to have a potential role in PCa pathogenesis by changing the glycosylation, protein stability, and PSA activity and may also affect the clinically measured F/T PSA ratio. Accounting for these effects on tPSA concentration and F/T PSA ratio may help to improve the accuracy of the current PSA test.
Ämnesord och genrebeteckningar
Biuppslag (personer, institutioner, konferenser, titlar ...)
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Stephens, CarsonQueensland University of Technology
(författare)
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Wilson, EmilyMonash University
(författare)
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Panchadsaram, JanaththaniQueensland University of Technology
(författare)
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DeVoss, KerryQML Pathology
(författare)
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Koistinen, HannuUniversity of Helsinki
(författare)
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Stenman, Ulf HåkanUniversity of Helsinki
(författare)
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Brook, Mark N.University of Cambridge
(författare)
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Buckle, Ashley M.Monash University
(författare)
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Klein, Robert J.Icahn School of Medicine at Mount Sinai
(författare)
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Lilja, HansLund University,Lunds universitet,Klinisk kemi, Malmö,Forskargrupper vid Lunds universitet,Clinical Chemistry, Malmö,Lund University Research Groups,Memorial Sloan-Kettering Cancer Center,University of Oxford(Swepub:lu)klke-hli
(författare)
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Clements, JudithQueensland University of Technology
(författare)
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Batra, JyotsnaQueensland University of Technology
(författare)
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Queensland University of TechnologyMonash University
(creator_code:org_t)
Sammanhörande titlar
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Ingår i:Clinical Chemistry: Oxford University Press (OUP)65:1, s. 1-90009-91471530-8561
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Srinivasan, Sril ...
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Stephens, Carson
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Wilson, Emily
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Panchadsaram, Ja ...
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DeVoss, Kerry
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Koistinen, Hannu
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Stenman, Ulf Håk ...
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Brook, Mark N.
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Buckle, Ashley M ...
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Klein, Robert J.
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Lilja, Hans
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Clements, Judith
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Batra, Jyotsna
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Lunds universitet