Differential alternative splicing of human transglutaminase 4 in benign prostate hyperplasia and prostate cancer

Exp Mol Med. 2010 Apr 30;42(4):310-8. doi: 10.3858/emm.2010.42.4.031.

Abstract

Transglutaminase 4 is a member of enzyme family that catalyzes calcium-dependent posttranslational modification of proteins. Although transglutaminase 4 has been shown to have prostate-restricted expression pattern, little is known about the biological function of transglutaminase 4 in human. To gain insight into its role in prostate, we analyzed the expression status of human transglutaminase 4 in benign prostate hyperplasia (BPH) and prostate cancer (PCa). Unexpectedly, RT-PCR and nucleotide sequence analysis showed four alternative splicing variants of transglutaminase 4: transglutaminase 4-L, -M (-M1 and -M2) and -S. The difference between transglutaminase 4-M1 and -M2 is attributed to splicing sites, but not nucleotide size. The deduced amino acid sequences showed that transglutaminase 4-L, -M1 and -M2 have correct open reading frames, whereas transglutaminase 4-S has a truncated reading frame. RT-PCR analysis of clinical samples revealed that transglutaminase 4-M and -S were detected in all tested prostate tissue (80 BPH and 48 PCa). Interestingly, transglutaminase 4-L was found in 56% of BPH (45 out of 80) and only in 15% of PCa (7 out of 48). However, transglutaminase 4-L expression did not correlate with serum prostate-specific antigen (PSA) level, prostate volumes or PSA densities. These results will provide a clue to future investigation aiming at delineating physiological and pathological roles of human transglutaminase 4.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Alternative Splicing / genetics*
  • Amino Acid Sequence
  • Base Sequence
  • Gene Expression Regulation, Neoplastic
  • HeLa Cells
  • Humans
  • Isoenzymes / chemistry
  • Isoenzymes / genetics
  • Isoenzymes / metabolism
  • Male
  • Molecular Sequence Data
  • Prostatic Hyperplasia / enzymology*
  • Prostatic Hyperplasia / genetics*
  • Prostatic Neoplasms / enzymology*
  • Prostatic Neoplasms / genetics*
  • Saccharomyces cerevisiae
  • Transglutaminases / chemistry
  • Transglutaminases / genetics*
  • Transglutaminases / metabolism

Substances

  • Isoenzymes
  • transglutaminase 4
  • Transglutaminases