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Transforming growth factor-β1 is not involved in TCDD-dependent release from contact inhibition in WB-F344 cells

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Abstract

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) 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 threefold increase in DNA synthesis when TCDD (1 nM) is applied to confluent cells. Since proliferation of epithelial cells is known to be inhibited by TGF-β, we investigated whether decreased TGF-β1 mediates TCDD-dependent release from contact inhibition in WB-F344 cells. Expression of TGF-β (type II) receptor in WB-F344 cells was analyzed by Western blot analysis. Exposure of 0.1 ng/ml TGF-β1 to exponentially growing WB-F344 cells resulted in a 40% decrease in DNA synthesis, which was blocked by preincubation with a neutralizing anti-TGF-β1 antibody, indicating that the TGF-β receptor in WB-F344 cells is functionally active. Preincubation of confluent, G1-arrested cultures with the neutralizing anti-TGF-β1-antibody did not lead to an increase in DNA synthesis, ruling out an involvement of TGF-β1 in mediating contact inhibition in WB-F344 cells. In accord with this, Western blot analysis revealed that protein expression of TGF-β1 is neither upregulated in confluent cultures nor decreased after TCDD treatment. We conclude that TGF-β1 is not involved in contact inhibition or in TCDD-dependent release from contact inhibition in WB-F344 cells.

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Acknowledgements

We thank K.-W. Bock for kindly providing us with the WB-F344 cells, Sandra Niemann for excellent technical assistance, and Carsten Weiss for fruitful discussions. This work is part of the M.D. thesis of P.H. and was supported by the grant Di 793/1-3 by the Deutsche Forschungsgemeinschaft.

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  1. Institute of Toxicology, Johannes Gutenberg-University, Obere Zahlbacherstrasse 67, 55131, Mainz, Germany

    Peter Hoelper, Dagmar Faust, Franz Oesch & Cornelia Dietrich

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  1. Peter Hoelper
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  2. Dagmar Faust
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  3. Franz Oesch
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  4. Cornelia Dietrich
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Correspondence to Cornelia Dietrich.

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Hoelper, P., Faust, D., Oesch, F. et al. Transforming growth factor-β1 is not involved in TCDD-dependent release from contact inhibition in WB-F344 cells. Arch Toxicol 79, 31–36 (2005). https://doi.org/10.1007/s00204-004-0601-0

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  • DOI: https://doi.org/10.1007/s00204-004-0601-0

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