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  Transforming growth factor beta as a potent promoter in two-stage BALB/c 3T3 cell transformation

Hamel, E., Katoh, F., Mueller, G., Birchmeier, W., & Yamasaki, H. (1988). Transforming growth factor beta as a potent promoter in two-stage BALB/c 3T3 cell transformation. Cancer Research, 48(10), 2832-2836.

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Hamel, E, Author
Katoh, F, Author
Mueller, G1, Author           
Birchmeier, W1, Author           
Yamasaki, H, Author
Affiliations:
1Birchmeier Group, Friedrich Miescher Laboratory, Max Planck Society, ou_3480812              

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 Abstract: We have tested transforming growth factor beta (TGF beta) in the two-stage BALB/c 3T3 cell transformation assay for possible tumor-promoting activity, since it has several effects similar to those of tumor-promoting phorbol esters. After initiation of BALB/c 3T3 cells with 3-methylchol-anthrene, treatment with TGF beta at 1 ng/ml alone or in combination with epidermal growth factor (EGF) for 4 weeks enhanced the number of transformed foci by 5- to 6-fold in comparison with uninitiated cells. Initiation treatment alone induced no or very few transformed foci in several assays. Treatment with phorbol-12,13-didecanoate (PDD) at 100 ng/ml for 4 weeks enhanced the number of transformed foci in initiated BALB/c 3T3 cells by 4- to 5-fold in comparison with uninitiated cells. Thus, TGF beta at 1 ng/ml is as potent as PDD at 100 ng/ml for tumor-promoting activity in the two-stage BALB/c 3T3 cell transformation assay. The enhancing effect of TGF beta was dose-related in the dose range tested (0.03-1 ng/ml) and was not reversible. Some of the foci induced by combined MCA-TGF beta-EGF treatment were cloned, and eight out of nine clones tested produced tumors in nude mice. TGF beta (1 ng/ml) plus EGF (2 ng/ml) increased the saturation density to a similar extent as PDD (100 ng/ml) but did not affect the growth of BALB/c 3T3 cells. We observed no change in junctional intercellular communication, as measured by the dye transfer method, when cells were treated with TGF beta during the two-stage BALB/c 3T3 cell transformation assay. Nevertheless, there was selective communication between transformed and surrounding nontransformed cells; MCA-TGF beta transformed cells intercommunicated among themselves but not with surrounding nontransformed cells. Our results indicate that TGF beta has potent tumor-promoting activity in vitro, but that this activity is not mediated by a complete blockage of intercellular communication, as is suggested for phorbol ester tumor promoters.

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 Dates: 1988-05
 Publication Status: Issued
 Pages: -
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 Rev. Type: -
 Identifiers: PMID: 3258789
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Title: Cancer Research
Source Genre: Journal
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Publ. Info: Baltimore, Md. : Waverly Press
Pages: - Volume / Issue: 48 (10) Sequence Number: - Start / End Page: 2832 - 2836 Identifier: ISSN: 0008-5472
CoNE: https://pure.mpg.de/cone/journals/resource/991042743115962_1