Increased expression of GCNT1 is associated with altered O-glycosylation of PSA, PAP, and MUC1 in human prostate cancers

Zuxiong Chen, Zulfiqar G. Gulzar, Catherine A. St. Hill, Bruce Walcheck, James D. Brooks

Research output: Contribution to journalArticlepeer-review

25 Scopus citations

Abstract

BACKGROUND Protein glycosylation is a common posttranslational modification and glycan structural changes have been observed in several malignancies including prostate cancer. We hypothesized that altered glycosylation could be related to differences in gene expression levels of glycoprotein synthetic enzymes between normal and malignant prostate tissues. METHODS We interrogated prostate cancer gene expression data for reproducible changes in expression of glycoprotein synthetic enzymes. Over-expression of GCNT1 was validated in prostate samples using RT-PCR. ELISA was used to measure core 2 O-linked glycan sialyl Lewis X (sLex) of prostate specific antigen (PSA), Mucin1 (MUC1), and prostatic acidic phosphatase (PAP) proteins. RESULTS A key glycosyltransferase, GCNT1, was consistently over-expressed in several prostate cancer gene expression datasets. RT-PCR confirmed increased transcript levels in cancer samples compared to normal prostate tissue in fresh-frozen prostate tissue samples. ELISA using PSA, PAP, and MUC1 capture antibodies and a specific core 2 O-linked sLex detection antibody demonstrated elevation of this glycan structure in cancer compared to normal tissues for MUC1 (P = 0.01), PSA (P = 0.03) and near significant differences in PAP sLex levels (P = 0.06). MUC1, PSA and PAP protein levels alone were not significantly different between paired normal and malignant prostate samples. CONCLUSIONS GCNT1 is over-expressed in prostate cancer and is associated with higher levels of core 2 O-sLex in PSA, PAP and MUC1 proteins. Alterations of O-linked glycosylation could be important in prostate cancer biology and could provide a new avenue for development of prostate cancer specific glycoprotein biomarkers. Prostate 74:1059-1067, 2014.

Original languageEnglish (US)
Pages (from-to)1059-1067
Number of pages9
JournalProstate
Volume74
Issue number10
DOIs
StatePublished - Jul 2014

Keywords

  • GCNT1
  • O-glycosylation
  • prostate cancer
  • sialyl Lewis X

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