Exp Mol Med.  2010 Apr;42(4):310-318. 10.3858/emm.2010.42.4.031.

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

• Cho SY
• Choi K
• Jeon JH
• Kim CW
• Shin DM
• Lee JB
• Lee SE
• Kim CS
• Park JS
• Jeong EM
• Jang GY
• Song KY
• Kim IG

• KMID: 983979
• DOI: http://doi.org/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.

Keyword

alternative splicing; prostate hyperplasia; prostatic neoplasms; transglutaminase 4