Transforming growth factor beta1 is not involved in 2,3,7,8-tetrachlorodibenzo- p-dioxin-dependent release from contact-inhibition in WB-F344 cells.
TCDD (2,3,7,8-tetrachlorodibenzo- p-dioxin) is the most potent tumor promoter ever tested in rodents. Although it is known that most of the effects of TCDD are mediated by binding to the aryl hydrocarbon receptor (AhR), the mechanisms leading to tumor promotion still remain to be elucidated. Loss of contact-inhibition is one characteristic hallmark in tumorigenesis. In WB-F344 cells, TCDD induces a release from contact-inhibition, which is manifested by a two- to three-fold increase in DNA-synthesis when TCDD (1 nM) is given to confluent cells. Since proliferation of epithelial cells is known to be inhibited by transforming growth factor beta (TGF-beta) we investigated whether decreased TGF-beta expression mediates TCDD-dependent release from contact-inhibition in WB-F344 cells. Expression of TGF-beta (type II) receptor in WB-F344 cells was shown by Western blot analysis. Exposure of exponentially growing WB-F344 cells to 0.1 ng/ml TGF-beta1 resulted in a 40% decrease in DNA synthesis, which could be blocked by pre-incubation with a neutralizing anti-TGF-beta1 antibody indicating that the TGF-beta receptor in WB-F344 cells is functionally active. Pre-incubation of confluent, G1-arrested cultures with the neutralizing anti-TGF-beta1 antibody did not lead to an increase in DNA synthesis, ruling out an involvement of TGF-beta1 in mediating contact-inhibition in WB-F344 cells. In accordance with this, Western blot analysis revealed that protein expression of TGF-beta1 was neither upregulated in confluent cultures nor decreased after TCDD treatment. We therefore conclude that TGF-beta1 is not involved in contact-inhibition nor in TCDD-dependent release from contact-inhibition in WB-F344 cells.
Institute of Toxicology, Johannes Gutenberg-University, Obere Zahlbacherstr. 67, 55131 Mainz, Germany.
Peter
P
Hoelper
Dagmar
D
Faust
Franz
F
Oesch
Cornelia
C
Dietrich
D000818:Animals; D015153:Blotting, Western; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects*; D004247:DNA / Q000096:biosynthesis; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism; D008099:Liver / Q000166:cytology*; D000072317:Polychlorinated Dibenzodioxins / Q000633:toxicity*; D051381:Rats; D018125:Receptors, Transforming Growth Factor beta / Q000096:biosynthesis; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D053773:Transforming Growth Factor beta1
D000072317:Polychlorinated Dibenzodioxins; D018125:Receptors, Transforming Growth Factor beta; C508962:Tgfb1 protein, rat; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D004247:DNA