MT1G hypermethylation is associated with higher tumor stage in prostate cancer

Rui Henrique, Carmen Jerónimo, Mohammad Hoque, Shuji Nomoto, André L. Carvalho, Vera L. Costa, Jorge Oliveira, Manuel R. Teixeira, Carlos Lopes, David Sidransky

Research output: Contribution to journalArticle

Abstract

Purpose: Zinc is involved in several physiologic processes, including cell growth and proliferation. Although in normal prostate tissue zinc levels are high, there is a marked decrease in prostate cancer. Metallothioneins control the bioavailability of zinc and one isoform, MT1G, was reported down-regulated in prostate cancer. Here, we investigated whether promoter methylation might cause MT1G silencing in prostate cancer. Patients and Methods: The MT1G promoter was assessed by quantitative methylation-specific PCR on prospectively collected tissue samples from 121 patients with prostate cancer, 39 paired high-grade prostatic intraepithelial neoplasias (HGPIN), 29 patients with benign prostatic hyperplasia, 13 normal prostate tissue samples from cystoprostatectomy specimens, and prostate cancer cell lines. The methylation levels were calculated and were correlated with clinical and pathologic variables. Reverse transcription-PCR was done in cell lines to assess MT1G mRNA expression before and after demethylating treatment. Results: MT1G promoter hypermethylation was found in 29 of 121 prostate cancer, 5 of 39 HGPIN, 3 of 29 benign prostatic hyperplasia, and 0 of 13 normal prostate tissue samples. No significant differences in methylation frequencies or levels were found (P = 0.057, for both). Methylation levels were found to correlate with tumor stage but not with Gleason grade. MT1G hypermethylation was more frequent in prostate cancer that spread beyond the prostate capsule. All prostate cancer cell lines tested showed MT1G promoter methylation, but no differences in expression were apparent after demethylation. Conclusions: Our findings suggest that MT1G promoter methylation is associated with tumor aggressiveness in prostate cancer and it might be a marker of locally advanced disease.

Original languageEnglish (US)
Pages (from-to)1274-1278
Number of pages5
JournalCancer Epidemiology Biomarkers and Prevention
Volume14
Issue number5
DOIs
StatePublished - May 2005

Fingerprint

Prostatic Neoplasms
Methylation
Prostate
Neoplasms
Prostatic Intraepithelial Neoplasia
Zinc
Prostatic Hyperplasia
Cell Line
Polymerase Chain Reaction
Metallothionein
Biological Availability
Reverse Transcription
Capsules
Protein Isoforms
Cell Proliferation
Messenger RNA

ASJC Scopus subject areas

  • Epidemiology
  • Oncology

Cite this

MT1G hypermethylation is associated with higher tumor stage in prostate cancer. / Henrique, Rui; Jerónimo, Carmen; Hoque, Mohammad; Nomoto, Shuji; Carvalho, André L.; Costa, Vera L.; Oliveira, Jorge; Teixeira, Manuel R.; Lopes, Carlos; Sidransky, David.

In: Cancer Epidemiology Biomarkers and Prevention, Vol. 14, No. 5, 05.2005, p. 1274-1278.

Research output: Contribution to journalArticle

Henrique, R, Jerónimo, C, Hoque, M, Nomoto, S, Carvalho, AL, Costa, VL, Oliveira, J, Teixeira, MR, Lopes, C & Sidransky, D 2005, 'MT1G hypermethylation is associated with higher tumor stage in prostate cancer', Cancer Epidemiology Biomarkers and Prevention, vol. 14, no. 5, pp. 1274-1278. https://doi.org/10.1158/1055-9965.EPI-04-0659
Henrique, Rui ; Jerónimo, Carmen ; Hoque, Mohammad ; Nomoto, Shuji ; Carvalho, André L. ; Costa, Vera L. ; Oliveira, Jorge ; Teixeira, Manuel R. ; Lopes, Carlos ; Sidransky, David. / MT1G hypermethylation is associated with higher tumor stage in prostate cancer. In: Cancer Epidemiology Biomarkers and Prevention. 2005 ; Vol. 14, No. 5. pp. 1274-1278.
@article{dd02c09f309e43ac9c60df1b26982306,
title = "MT1G hypermethylation is associated with higher tumor stage in prostate cancer",
abstract = "Purpose: Zinc is involved in several physiologic processes, including cell growth and proliferation. Although in normal prostate tissue zinc levels are high, there is a marked decrease in prostate cancer. Metallothioneins control the bioavailability of zinc and one isoform, MT1G, was reported down-regulated in prostate cancer. Here, we investigated whether promoter methylation might cause MT1G silencing in prostate cancer. Patients and Methods: The MT1G promoter was assessed by quantitative methylation-specific PCR on prospectively collected tissue samples from 121 patients with prostate cancer, 39 paired high-grade prostatic intraepithelial neoplasias (HGPIN), 29 patients with benign prostatic hyperplasia, 13 normal prostate tissue samples from cystoprostatectomy specimens, and prostate cancer cell lines. The methylation levels were calculated and were correlated with clinical and pathologic variables. Reverse transcription-PCR was done in cell lines to assess MT1G mRNA expression before and after demethylating treatment. Results: MT1G promoter hypermethylation was found in 29 of 121 prostate cancer, 5 of 39 HGPIN, 3 of 29 benign prostatic hyperplasia, and 0 of 13 normal prostate tissue samples. No significant differences in methylation frequencies or levels were found (P = 0.057, for both). Methylation levels were found to correlate with tumor stage but not with Gleason grade. MT1G hypermethylation was more frequent in prostate cancer that spread beyond the prostate capsule. All prostate cancer cell lines tested showed MT1G promoter methylation, but no differences in expression were apparent after demethylation. Conclusions: Our findings suggest that MT1G promoter methylation is associated with tumor aggressiveness in prostate cancer and it might be a marker of locally advanced disease.",
author = "Rui Henrique and Carmen Jer{\'o}nimo and Mohammad Hoque and Shuji Nomoto and Carvalho, {Andr{\'e} L.} and Costa, {Vera L.} and Jorge Oliveira and Teixeira, {Manuel R.} and Carlos Lopes and David Sidransky",
year = "2005",
month = "5",
doi = "10.1158/1055-9965.EPI-04-0659",
language = "English (US)",
volume = "14",
pages = "1274--1278",
journal = "Cancer Epidemiology Biomarkers and Prevention",
issn = "1055-9965",
publisher = "American Association for Cancer Research Inc.",
number = "5",

}

TY - JOUR

T1 - MT1G hypermethylation is associated with higher tumor stage in prostate cancer

AU - Henrique, Rui

AU - Jerónimo, Carmen

AU - Hoque, Mohammad

AU - Nomoto, Shuji

AU - Carvalho, André L.

AU - Costa, Vera L.

AU - Oliveira, Jorge

AU - Teixeira, Manuel R.

AU - Lopes, Carlos

AU - Sidransky, David

PY - 2005/5

Y1 - 2005/5

N2 - Purpose: Zinc is involved in several physiologic processes, including cell growth and proliferation. Although in normal prostate tissue zinc levels are high, there is a marked decrease in prostate cancer. Metallothioneins control the bioavailability of zinc and one isoform, MT1G, was reported down-regulated in prostate cancer. Here, we investigated whether promoter methylation might cause MT1G silencing in prostate cancer. Patients and Methods: The MT1G promoter was assessed by quantitative methylation-specific PCR on prospectively collected tissue samples from 121 patients with prostate cancer, 39 paired high-grade prostatic intraepithelial neoplasias (HGPIN), 29 patients with benign prostatic hyperplasia, 13 normal prostate tissue samples from cystoprostatectomy specimens, and prostate cancer cell lines. The methylation levels were calculated and were correlated with clinical and pathologic variables. Reverse transcription-PCR was done in cell lines to assess MT1G mRNA expression before and after demethylating treatment. Results: MT1G promoter hypermethylation was found in 29 of 121 prostate cancer, 5 of 39 HGPIN, 3 of 29 benign prostatic hyperplasia, and 0 of 13 normal prostate tissue samples. No significant differences in methylation frequencies or levels were found (P = 0.057, for both). Methylation levels were found to correlate with tumor stage but not with Gleason grade. MT1G hypermethylation was more frequent in prostate cancer that spread beyond the prostate capsule. All prostate cancer cell lines tested showed MT1G promoter methylation, but no differences in expression were apparent after demethylation. Conclusions: Our findings suggest that MT1G promoter methylation is associated with tumor aggressiveness in prostate cancer and it might be a marker of locally advanced disease.

AB - Purpose: Zinc is involved in several physiologic processes, including cell growth and proliferation. Although in normal prostate tissue zinc levels are high, there is a marked decrease in prostate cancer. Metallothioneins control the bioavailability of zinc and one isoform, MT1G, was reported down-regulated in prostate cancer. Here, we investigated whether promoter methylation might cause MT1G silencing in prostate cancer. Patients and Methods: The MT1G promoter was assessed by quantitative methylation-specific PCR on prospectively collected tissue samples from 121 patients with prostate cancer, 39 paired high-grade prostatic intraepithelial neoplasias (HGPIN), 29 patients with benign prostatic hyperplasia, 13 normal prostate tissue samples from cystoprostatectomy specimens, and prostate cancer cell lines. The methylation levels were calculated and were correlated with clinical and pathologic variables. Reverse transcription-PCR was done in cell lines to assess MT1G mRNA expression before and after demethylating treatment. Results: MT1G promoter hypermethylation was found in 29 of 121 prostate cancer, 5 of 39 HGPIN, 3 of 29 benign prostatic hyperplasia, and 0 of 13 normal prostate tissue samples. No significant differences in methylation frequencies or levels were found (P = 0.057, for both). Methylation levels were found to correlate with tumor stage but not with Gleason grade. MT1G hypermethylation was more frequent in prostate cancer that spread beyond the prostate capsule. All prostate cancer cell lines tested showed MT1G promoter methylation, but no differences in expression were apparent after demethylation. Conclusions: Our findings suggest that MT1G promoter methylation is associated with tumor aggressiveness in prostate cancer and it might be a marker of locally advanced disease.

UR - http://www.scopus.com/inward/record.url?scp=20844459807&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=20844459807&partnerID=8YFLogxK

U2 - 10.1158/1055-9965.EPI-04-0659

DO - 10.1158/1055-9965.EPI-04-0659

M3 - Article

C2 - 15894685

AN - SCOPUS:20844459807

VL - 14

SP - 1274

EP - 1278

JO - Cancer Epidemiology Biomarkers and Prevention

JF - Cancer Epidemiology Biomarkers and Prevention

SN - 1055-9965

IS - 5

ER -