Dioxin induces transforming growth factor-alpha in human keratinocytes.
2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD), a widespread environmental toxicant, is a tumor promoter that induces hyperplasia in epithelial cells. Exposure of cultured human keratinocytes to TCDD, resulted in a time-dependent dioxin-specific Ah receptor-mediated release of transforming growth factor-alpha (TGF-alpha) into the culture medium. Cultures exposed to TCDD showed a rate of TGF-alpha secretion into the medium of about 30 fmol/ml/day, as well as a 3- to 6-fold increase in TGF-alpha mRNA expression. Increased production of TGF-alpha in human keratinocytes exposed to TCDD demonstrates a modulation of autocrine regulation in those cells. These results suggest that induction of TGF-alpha could be an important part of the mechanism of dioxin-mediated toxicity and tumor promotion.
Choi
E J
EJ
Division of Environmental and Occupational Health, University of Minnesota, Minneapolis 55455.
Toscano
D G
DG
Ryan
J A
JA
Riedel
N
N
Toscano
W A
WA
D015152:Blotting, Northern; D015153:Blotting, Western; D002273:Carcinogens; D004815:Epidermal Growth Factor / Q000378:metabolism; D066246:ErbB Receptors / Q000378:metabolism; D006801:Humans; D015603:Keratinocytes / Q000378:metabolism*; D010766:Phosphorylation; D000072317:Polychlorinated Dibenzodioxins / Q000633:toxicity*; D012333:RNA, Messenger / Q000032:analysis; D016211:Transforming Growth Factor alpha / Q000378:metabolism*
D002273:Carcinogens; D000072317:Polychlorinated Dibenzodioxins; D012333:RNA, Messenger; D016211:Transforming Growth Factor alpha; D004815:Epidermal Growth Factor; D066246:ErbB Receptors