SwePub
Sök i LIBRIS databas

  Utökad sökning

onr:"swepub:oai:lup.lub.lu.se:fe87050f-7dea-4b49-98f2-d878f3ace6f2"
 

Sökning: onr:"swepub:oai:lup.lub.lu.se:fe87050f-7dea-4b49-98f2-d878f3ace6f2" > Prostate cancer ris...

Prostate cancer risk-associated single-nucleotide polymorphism affects prostate-specific antigen glycosylation and its function

Srinivasan, Srilakshmi (författare)
Queensland University of Technology
Stephens, Carson (författare)
Queensland University of Technology
Wilson, Emily (författare)
Monash University
visa fler...
Panchadsaram, Janaththani (författare)
Queensland University of Technology
DeVoss, Kerry (författare)
QML Pathology
Koistinen, Hannu (författare)
University of Helsinki
Stenman, Ulf Håkan (författare)
University of Helsinki
Brook, Mark N. (författare)
University of Cambridge
Buckle, Ashley M. (författare)
Monash University
Klein, Robert J. (författare)
Icahn School of Medicine at Mount Sinai
Lilja, Hans (författare)
Lund 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
Clements, Judith (författare)
Queensland University of Technology
Batra, Jyotsna (författare)
Queensland University of Technology
visa färre...
 (creator_code:org_t)
American Association for Clinical Chemistry, 2019
2019
Engelska.
Ingår i: Clinical Chemistry. - : American Association for Clinical Chemistry. - 0009-9147. ; 65:1, s. 1-9
  • Tidskriftsartikel (refereegranskat)
Abstract Ämnesord
Stäng  
  • 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

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Medicinsk genetik (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Medical Genetics (hsv//eng)
MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Basic Medicine (hsv//eng)

Publikations- och innehållstyp

ref (ämneskategori)
art (ämneskategori)

Hitta via bibliotek

Till lärosätets databas

Kungliga biblioteket hanterar dina personuppgifter i enlighet med EU:s dataskyddsförordning (2018), GDPR. Läs mer om hur det funkar här.
Så här hanterar KB dina uppgifter vid användning av denna tjänst.

 
pil uppåt Stäng

Kopiera och spara länken för att återkomma till aktuell vy