title: DNA methylation of estrogen receptor alpha gene by phthalates.
abstract: The phthalates are ubiquitous industrial plasticizers and include agents such as di(2-ethylhexyl) phthalate (DEHP), dibutyl phthalate (DBP), and butyl benzyl phthalate (BBP), which are classified as endocrine disruptors because of their anti-androgenic or pro-estrogenic effects. A recent study suggested that DBP produced the hypomethylation of c-myc protooncogene in mouse liver to activate c-myc. In the present study, DNA hypomethylation at the promoter region of the estrogen receptor alpha (ERalpha) gene was investigated by methylation-specific polymerase chain reaction (MSP) in a human breast cancer (MCF7) and in a normal (MCF10A) cell line after DBP treatment. Yeast-based estrogen receptor transcription assays showed that hERalpha gene expression was induced by BBP but not DBP. Moreover, MCF7 cells treated with BBP or DBP at 10(-5)M led to the demethylation of ERalpha promoter-associated CpG islands. These data suggest that an altered ER mRNA expression by BBP might be related to aberrant DNA methylation in the promoter region of ERalpha.
authors.affiliation: Division of Toxicology, School of Pharmacy, SungKyunKwan University, Jangan-Gu, Suwon, Kyonggi-do, Korea.
authors.forename: Se Chan
authors.initials: SC
authors.lastname: Kang
authors.forename: Byung Mu
authors.initials: BM
authors.lastname: Lee
mesh_terms: D002460:Cell Line; D045744:Cell Line, Tumor; D018899:CpG Islands; D019175:DNA Methylation; D018076:DNA, Complementary / Q000378:metabolism; D003993:Dibutyl Phthalate / Q000633:toxicity; D004051:Diethylhexyl Phthalate / Q000633:toxicity; D047628:Estrogen Receptor alpha / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D010795:Phthalic Acids / Q000633:toxicity*; D010968:Plasticizers / Q000633:toxicity*; D012441:Saccharomyces cerevisiae / Q000378:metabolism; D001616:beta-Galactosidase / Q000378:metabolism
chemical_list: D018076:DNA, Complementary; D047628:Estrogen Receptor alpha; D010795:Phthalic Acids; D010968:Plasticizers; D003993:Dibutyl Phthalate; D004051:Diethylhexyl Phthalate; D001616:beta-Galactosidase; C027561:butylbenzyl phthalate