The important role of glycine N-methyltransferase in the carcinogenesis and progression of prostate cancer.

Abstract

Glycine N-methyltransferase (GNMT) has a role in the metabolism of methionine as well as in gluconeogenesis. It has recently been reported that the GNMT gene acts as a tumor-susceptible gene. However, little is known about the specific function of GNMT in carcinogenesis and malignant progression. To better our understanding of the function of GNMT in prostate cancer, we used siRNAs to examine the effects of GNMT knockdown on cell proliferation and the cell cycle. In addition, the relation between immunohistochemical GNMT expression and clinicopathologic parameters was investigated in 148 prostate cancer tissues. Here, we show that siRNA-mediated GNMT knockdown results in an inhibition of proliferation, and induces G1 arrest and apoptosis in prostate cancer cell lines. Moreover, high cytoplasmic GNMT expression was also correlated with a higher Gleason score (P<0.001) and higher pT stage (P=0.027). The patients with high GNMT cytoplasmic expression showed significantly lower disease-free survival rates than patients with low expression (P<0.001). High GNMT cytoplasmic expression had a significant impact on patient disease-free survival in multivariate analysis (P=0.005). This is the first investigation to reveal the novel finding that GNMT may have an important role in promoting prostate cancer cell growth via the regulation of apoptosis and contribute to the progression of prostate cancer. The modulation of GNMT expression or function may be a strategy for developing novel therapeutics for prostate cancer. GNMT may represent a novel marker of malignant progression and poor prognosis in prostate cancer.

• Authors: Yoo Hyun Song, Masaki Shiota, Kentaro Kuroiwa, Seiji Naito, Yoshinao Oda
• Journal: Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc (Mod Pathol) Vol. 24 Issue 9 Pg. 1272-80 (Sep 2011) ISSN: 1530-0285 [Electronic] United States
• PMID: 21572396 (Publication Type: Journal Article)

Chemical References

• Biomarkers, Tumor
• RNA, Small Interfering
• Glycine N-Methyltransferase

Topics

• Aged
• Biomarkers, Tumor (analysis)
• Blotting, Western
• Cell Cycle (physiology)
• Cell Line, Tumor
• Cell Proliferation
• Cell Separation
• Disease Progression
• Flow Cytometry
• Gene Knockdown Techniques
• Glycine N-Methyltransferase (metabolism)
• Humans
• Male
• Middle Aged
• Neoplasm Staging
• Prognosis
• Prostatic Neoplasms (enzymology, pathology)
• RNA, Small Interfering