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

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.

• Authors: Sung-Yup Cho, Kyungho Choi, Ju-Hong Jeon, Chai-Wan Kim, Dong-Myung Shin, Jong Bouk Lee, Sang Eun Lee, Choung-Soo Kim, Jeong-Soo Park, Eui Man Jeong, Gi-Yong Jang, Kye-Yong Song, In-Gyu Kim
• Journal: Experimental & molecular medicine (Exp Mol Med) Vol. 42 Issue 4 Pg. 310-8 (Apr 30 2010) ISSN: 2092-6413 [Electronic] United States
• PMID: 20177144 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Isoenzymes
• transglutaminase 4
• Transglutaminases

Topics

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