DNA methylation of estrogen receptor alpha gene by phthalates.
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.
Kang
Se Chan
SC
Division of Toxicology, School of Pharmacy, SungKyunKwan University, Jangan-Gu, Suwon, Kyonggi-do, Korea.
Lee
Byung Mu
BM
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
D018076:DNA, Complementary; D047628:Estrogen Receptor alpha; D010795:Phthalic Acids; D010968:Plasticizers; D003993:Dibutyl Phthalate; D004051:Diethylhexyl Phthalate; D001616:beta-Galactosidase; C027561:butylbenzyl phthalate