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

Yoo Hyun Song, Masaki Shiota, Kentaro Kuroiwa, Seiji Naito, Yoshinao Oda

Research output: Contribution to journalArticle

36 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1272-1280
Number of pages9
JournalModern Pathology
Volume24
Issue number9
DOIs
Publication statusPublished - Sep 1 2011

Fingerprint

Glycine N-Methyltransferase
Prostatic Neoplasms
Carcinogenesis
Disease-Free Survival
Apoptosis
Gluconeogenesis
Neoplasm Grading

All Science Journal Classification (ASJC) codes

  • Pathology and Forensic Medicine

Cite this

The important role of glycine N-methyltransferase in the carcinogenesis and progression of prostate cancer. / Song, Yoo Hyun; Shiota, Masaki; Kuroiwa, Kentaro; Naito, Seiji; Oda, Yoshinao.

In: Modern Pathology, Vol. 24, No. 9, 01.09.2011, p. 1272-1280.

Research output: Contribution to journalArticle

@article{8b1f698b20e849eaae7c6766ca006947,
title = "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.",
author = "Song, {Yoo Hyun} and Masaki Shiota and Kentaro Kuroiwa and Seiji Naito and Yoshinao Oda",
year = "2011",
month = "9",
day = "1",
doi = "10.1038/modpathol.2011.76",
language = "English",
volume = "24",
pages = "1272--1280",
journal = "Modern Pathology",
issn = "0893-3952",
publisher = "Nature Publishing Group",
number = "9",

}

TY - JOUR

T1 - The important role of glycine N-methyltransferase in the carcinogenesis and progression of prostate cancer

AU - Song, Yoo Hyun

AU - Shiota, Masaki

AU - Kuroiwa, Kentaro

AU - Naito, Seiji

AU - Oda, Yoshinao

PY - 2011/9/1

Y1 - 2011/9/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=80052423473&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=80052423473&partnerID=8YFLogxK

U2 - 10.1038/modpathol.2011.76

DO - 10.1038/modpathol.2011.76

M3 - Article

C2 - 21572396

AN - SCOPUS:80052423473

VL - 24

SP - 1272

EP - 1280

JO - Modern Pathology

JF - Modern Pathology

SN - 0893-3952

IS - 9

ER -