Estrogen-responsive genes newly found to be modified by TCDD exposure in human cell lines and mouse systems.
2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) can induce estrogenic action or inhibit estrogen-induced effects in various tissues because of aryl hydrocarbon receptor (AhR)-estrogen receptor (ER) cross-talk. In order to identify the biomarkers of TCDD endocrine disruption, we screened estrogen-responsive genes modified by TCDD exposure using specific cDNA microarrays spotted with estrogen-responsive genes. MCF-7 human breast carcinoma cells and RL95-2 human endometrial carcinoma cells were exposed to TCDD, and an analysis of their gene expression revealed 32 genes exhibiting a significant change. The mRNA expression levels of 27 genes were subsequently verified using real-time RT-PCR. Among these genes, bioinformatic analyses indicated that insulin-like growth factor-binding protein 5 (IGFBP5) gene expression might be influenced by estrogen status. In our animal experiments, IGFBP5 was also shown to be responsive to TCDD exposure in mouse fetuses in utero. These results suggest that TCDD affects the expression levels of a series of estrogen-responsive genes, and follow-up fetal studies in mice indicated that IGFBP5 is useful as a biomarker of TCDD activity.
Tanaka
Junko
J
Research Center for Environmental Risk, National Institute for Environmental Studies, 16-2 Onogawa, Tsukuba 305-8506, Japan.
Yonemoto
Junzo
J
Zaha
Hiroko
H
Kiyama
Ryoiti
R
Sone
Hideko
H
D000818:Animals; D045744:Cell Line, Tumor; D016000:Cluster Analysis; D004781:Environmental Exposure; D004785:Environmental Pollutants / Q000494:pharmacology; D004967:Estrogens / Q000494:pharmacology*; D005260:Female; D005333:Fetus / Q000187:drug effects / Q000378:metabolism; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects*; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D000072317:Polychlorinated Dibenzodioxins / Q000494:pharmacology*; D011247:Pregnancy; D020133:Reverse Transcriptase Polymerase Chain Reaction
D004785:Environmental Pollutants; D004967:Estrogens; D000072317:Polychlorinated Dibenzodioxins