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

Journal Article · Thu Aug 15 04:00:00 EDT 1996 · Cancer Research

OSTI ID:602803

Issa, J P.J.; Baylin, S B; Belinsky, S A ^[1]

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1. Johns Hopkins Univ. School of Medicine, Baltimore, MD (United States)

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. 39 refs., 4 figs.

• DOE Contract Number: AC04-76EV01013
• OSTI ID: 602803
• Journal Information: Cancer Research, Journal Name: Cancer Research Vol. 56; ISSN 0008-5472; ISSN CNREA8
• Country of Publication: United States
• Language: English

Related Subjects

55 BIOLOGY AND MEDICINE
BASIC STUDIES
56 BIOLOGY AND MEDICINE
APPLIED STUDIES
CARCINOGENESIS
CARCINOGENS
CHRONIC EXPOSURE
ENVIRONMENTAL EXPOSURE
GENE MUTATIONS
GENE REGULATION
GENE REPRESSORS
GENES
GENETIC EFFECTS
LUNGS
METHYLATION
NEOPLASMS
NUCLEOTIDES
PLUTONIUM
POLYMERASE CHAIN REACTION
RODENTS
SPONTANEOUS MUTATIONS
TOBACCO SMOKES
TUMOR CELLS