DNA methylation-associated inactivation of TGFβ-related genes DRM/Gremlin, RUNX3, and HPP1 in human cancers

M. Suzuki, H. Shigematsu, D. S. Shames, N. Sunaga, T. Takahashi, N. Shivapurkar, T. Iizasa, E. P. Frenkel, J. D. Minna, T. Fujisawa, A. F. Gazdar

Research output: Contribution to journalArticle

67 Citations (Scopus)

Abstract

The transforming growth factor β (TGFβ)-signalling pathway is deregulated in many cancers. We examined the role of gene silencing via aberrant methylation of DRM/Gremlin and HPP1, which inhibit TGFβ signalling, and RUNX3, which facilitates TGFβ-signalling, of all genes that are thought to be tumour suppressors, are aberrantly expressed, and are thus thought to have important role in human cancers. We examined DRM/Gremlin mRNA expression in 44 cell lines and the promoter methylation status of DRM/Gremlin, HPP1, and RUNX3 in 44 cell lines and 511 primary tumours. The loss of DRM/Gremlin mRNA expression in human cancer cell lines is associated with DNA methylation, and treatment with the methylation inhibitor-reactivated mRNA expression (n=13). Methylation percentages of the three genes ranged from 0-83% in adult tumours and 0-50% in paediatric tumours. Methylation of DRM/Gremlin was more frequent in lung tumours in smokers, and methylation of all three genes was inversely correlated with prognosis in patients with bladder or prostate cancer. Our results provide strong evidence that these TGFβ-related genes are frequently deregulated through aberrant methylation in many human malignancies.

Original languageEnglish (US)
Pages (from-to)1029-1037
Number of pages9
JournalBritish Journal of Cancer
Volume93
Issue number9
DOIs
StatePublished - Oct 31 2005

Fingerprint

Transforming Growth Factors
DNA Methylation
Methylation
Genes
Neoplasms
Cell Line
Messenger RNA
Gene Silencing
Urinary Bladder Neoplasms
Prostatic Neoplasms
Pediatrics
Lung

Keywords

  • DRM/Gremlin (CKTSF1B1)
  • HPP1
  • Methylation
  • RUNX3
  • TGFβ

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

DNA methylation-associated inactivation of TGFβ-related genes DRM/Gremlin, RUNX3, and HPP1 in human cancers. / Suzuki, M.; Shigematsu, H.; Shames, D. S.; Sunaga, N.; Takahashi, T.; Shivapurkar, N.; Iizasa, T.; Frenkel, E. P.; Minna, J. D.; Fujisawa, T.; Gazdar, A. F.

In: British Journal of Cancer, Vol. 93, No. 9, 31.10.2005, p. 1029-1037.

Research output: Contribution to journalArticle

Suzuki, M, Shigematsu, H, Shames, DS, Sunaga, N, Takahashi, T, Shivapurkar, N, Iizasa, T, Frenkel, EP, Minna, JD, Fujisawa, T & Gazdar, AF 2005, 'DNA methylation-associated inactivation of TGFβ-related genes DRM/Gremlin, RUNX3, and HPP1 in human cancers', British Journal of Cancer, vol. 93, no. 9, pp. 1029-1037. https://doi.org/10.1038/sj.bjc.6602837
Suzuki, M. ; Shigematsu, H. ; Shames, D. S. ; Sunaga, N. ; Takahashi, T. ; Shivapurkar, N. ; Iizasa, T. ; Frenkel, E. P. ; Minna, J. D. ; Fujisawa, T. ; Gazdar, A. F. / DNA methylation-associated inactivation of TGFβ-related genes DRM/Gremlin, RUNX3, and HPP1 in human cancers. In: British Journal of Cancer. 2005 ; Vol. 93, No. 9. pp. 1029-1037.
@article{b1c6847b83fc462797da9dff40c3171e,
title = "DNA methylation-associated inactivation of TGFβ-related genes DRM/Gremlin, RUNX3, and HPP1 in human cancers",
abstract = "The transforming growth factor β (TGFβ)-signalling pathway is deregulated in many cancers. We examined the role of gene silencing via aberrant methylation of DRM/Gremlin and HPP1, which inhibit TGFβ signalling, and RUNX3, which facilitates TGFβ-signalling, of all genes that are thought to be tumour suppressors, are aberrantly expressed, and are thus thought to have important role in human cancers. We examined DRM/Gremlin mRNA expression in 44 cell lines and the promoter methylation status of DRM/Gremlin, HPP1, and RUNX3 in 44 cell lines and 511 primary tumours. The loss of DRM/Gremlin mRNA expression in human cancer cell lines is associated with DNA methylation, and treatment with the methylation inhibitor-reactivated mRNA expression (n=13). Methylation percentages of the three genes ranged from 0-83{\%} in adult tumours and 0-50{\%} in paediatric tumours. Methylation of DRM/Gremlin was more frequent in lung tumours in smokers, and methylation of all three genes was inversely correlated with prognosis in patients with bladder or prostate cancer. Our results provide strong evidence that these TGFβ-related genes are frequently deregulated through aberrant methylation in many human malignancies.",
keywords = "DRM/Gremlin (CKTSF1B1), HPP1, Methylation, RUNX3, TGFβ",
author = "M. Suzuki and H. Shigematsu and Shames, {D. S.} and N. Sunaga and T. Takahashi and N. Shivapurkar and T. Iizasa and Frenkel, {E. P.} and Minna, {J. D.} and T. Fujisawa and Gazdar, {A. F.}",
year = "2005",
month = "10",
day = "31",
doi = "10.1038/sj.bjc.6602837",
language = "English (US)",
volume = "93",
pages = "1029--1037",
journal = "British Journal of Cancer",
issn = "0007-0920",
publisher = "Nature Publishing Group",
number = "9",

}

TY - JOUR

T1 - DNA methylation-associated inactivation of TGFβ-related genes DRM/Gremlin, RUNX3, and HPP1 in human cancers

AU - Suzuki, M.

AU - Shigematsu, H.

AU - Shames, D. S.

AU - Sunaga, N.

AU - Takahashi, T.

AU - Shivapurkar, N.

AU - Iizasa, T.

AU - Frenkel, E. P.

AU - Minna, J. D.

AU - Fujisawa, T.

AU - Gazdar, A. F.

PY - 2005/10/31

Y1 - 2005/10/31

N2 - The transforming growth factor β (TGFβ)-signalling pathway is deregulated in many cancers. We examined the role of gene silencing via aberrant methylation of DRM/Gremlin and HPP1, which inhibit TGFβ signalling, and RUNX3, which facilitates TGFβ-signalling, of all genes that are thought to be tumour suppressors, are aberrantly expressed, and are thus thought to have important role in human cancers. We examined DRM/Gremlin mRNA expression in 44 cell lines and the promoter methylation status of DRM/Gremlin, HPP1, and RUNX3 in 44 cell lines and 511 primary tumours. The loss of DRM/Gremlin mRNA expression in human cancer cell lines is associated with DNA methylation, and treatment with the methylation inhibitor-reactivated mRNA expression (n=13). Methylation percentages of the three genes ranged from 0-83% in adult tumours and 0-50% in paediatric tumours. Methylation of DRM/Gremlin was more frequent in lung tumours in smokers, and methylation of all three genes was inversely correlated with prognosis in patients with bladder or prostate cancer. Our results provide strong evidence that these TGFβ-related genes are frequently deregulated through aberrant methylation in many human malignancies.

AB - The transforming growth factor β (TGFβ)-signalling pathway is deregulated in many cancers. We examined the role of gene silencing via aberrant methylation of DRM/Gremlin and HPP1, which inhibit TGFβ signalling, and RUNX3, which facilitates TGFβ-signalling, of all genes that are thought to be tumour suppressors, are aberrantly expressed, and are thus thought to have important role in human cancers. We examined DRM/Gremlin mRNA expression in 44 cell lines and the promoter methylation status of DRM/Gremlin, HPP1, and RUNX3 in 44 cell lines and 511 primary tumours. The loss of DRM/Gremlin mRNA expression in human cancer cell lines is associated with DNA methylation, and treatment with the methylation inhibitor-reactivated mRNA expression (n=13). Methylation percentages of the three genes ranged from 0-83% in adult tumours and 0-50% in paediatric tumours. Methylation of DRM/Gremlin was more frequent in lung tumours in smokers, and methylation of all three genes was inversely correlated with prognosis in patients with bladder or prostate cancer. Our results provide strong evidence that these TGFβ-related genes are frequently deregulated through aberrant methylation in many human malignancies.

KW - DRM/Gremlin (CKTSF1B1)

KW - HPP1

KW - Methylation

KW - RUNX3

KW - TGFβ

UR - http://www.scopus.com/inward/record.url?scp=27644455870&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=27644455870&partnerID=8YFLogxK

U2 - 10.1038/sj.bjc.6602837

DO - 10.1038/sj.bjc.6602837

M3 - Article

VL - 93

SP - 1029

EP - 1037

JO - British Journal of Cancer

JF - British Journal of Cancer

SN - 0007-0920

IS - 9

ER -