Methylation of the estrogen receptor CpG island in lung tumors is related to the specific type of carcinogen exposure

Jean Pierre J Issa, Stephen B Baylin, Steven A. Belinsky

Research output: Contribution to journalArticle

Abstract

Promoter methylation has recently been shown to be an alternative to mutation in inactivating tumor suppressor genes in human neoplasia. Although specific carcinogen exposures have been associated with characteristic mutation patterns in genes, the factors that lead to promoter hypermethylation remain unknown. One gene target for inactivation through promoter methylation is the estrogen receptor (ER). The purpose of this investigation was to determine the methylation status of this gene in lung tumors from smokers and those who never smoked and in rodents exposed to specific environmental carcinogens. Promoter methylation at the ER locus was detected in 4 of 11 tumors from never-smokers (36.4%) and 7 of 35 tumors from smokers (20%, P <0.001). Lung tumors induced by the tobacco-derived carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone also had a low incidence (16.7%) of ER methylation. In marked contrast, spontaneous and plutonium-induced tumors had a very high (81.8%) incidence of ER methylation. X-ray-induced tumors had an intermediate frequency of ER methylation (38.1%). The presence of ER methylation was associated with absent ER expression in rodent lung cancer cell lines. These results show for the first time that gene-specific promoter methylation can be modulated differentially depending on carcinogen exposure.

Original languageEnglish (US)
Pages (from-to)3655-3658
Number of pages4
JournalCancer Research
Volume56
Issue number16
StatePublished - Aug 15 1996

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CpG Islands
Estrogen Receptors
Carcinogens
Methylation
Lung
Neoplasms
Rodentia
Environmental Carcinogens
Genes
Plutonium
Mutation
Incidence
Gene Silencing
Tumor Suppressor Genes
Tobacco
Lung Neoplasms
X-Rays
Cell Line

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Methylation of the estrogen receptor CpG island in lung tumors is related to the specific type of carcinogen exposure. / Issa, Jean Pierre J; Baylin, Stephen B; Belinsky, Steven A.

In: Cancer Research, Vol. 56, No. 16, 15.08.1996, p. 3655-3658.

Research output: Contribution to journalArticle

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