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Type beta transforming growth factor: a bifunctional regulator of cellular growth.
Open accessAbstract
Type beta transforming growth factor (TGF-beta) is a two-chain polypeptide of 25,000 daltons isolated from many tissues, including bovine kidney, human placenta, and human platelets. It has been characterized by its ability to stimulate reversible transformation of nonneoplastic murine fibroblasts, as measured by the formation of colonies of these cells in soft agar (ED50 = 4 pM TGF-beta for NRK fibroblasts). We now show that the response of cells to TGF-beta is bifunctional, in that TGF-beta inhibits the anchorage-dependent growth of NRK fibroblasts and of human tumor cells by increasing cell cycle time. Moreover, the anchorage-independent growth of many human melanoma, lung carcinoma, and breast carcinoma cell lines is inhibited by TGF-beta at concentrations in the same range as those that stimulate colony formation of NRK fibroblasts (average ED50 = 10-30 pM TGF-beta for inhibition). Whereas epidermal growth factor and TGF-beta synergize to induce anchorage-independent growth of NRK fibroblasts, their effects on the growth of A-549 human lung carcinoma cells are antagonistic. The bifunctional response of cells to TGF-beta is further demonstrated in Fischer rat 3T3 fibroblasts transfected with a cellular myc gene. In these cells TGF-beta synergizes with platelet-derived growth factor to stimulate colony formation but inhibits the colony formation induced by epidermal growth factor. The data indicate that the effects of TGF-beta on cells are not a function of the peptide itself, but rather of the total set of growth factors and their receptors that is operant in the cell at a given time.
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Cites
Tumorigenic conversion of primary embryo fibroblasts requires at least two cooperating oncogenes
Land, H., Parada, L. F., & Weinberg, R. A. (1983) · Nature · doi:10.1038/304596a0 · Cited by 2,804
Cited by
Ignotz, R. A., & Massagué, J. (1986) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)35666-1 · Cited by 2,492
Chemically defined conditions for human iPSC derivation and culture
Chen, G., Gulbranson, D. R., Hou, Z., Bolin, J. M., Ruotti, V., Probasco, M. D., Smuga-Otto, K., Howden, S. E., Diol, N. R., Propson, N. E., et al. (2011) · Nature Methods · doi:10.1038/nmeth.1593 · Cited by 1,447
TGF-β and the TGF-β family: context-dependent roles in cell and tissue physiology
Morikawa, M., Derynck, R., & Miyazono, K. (2016) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a021873 · Cited by 1,321
Contextual determinants of TGFβ action in development, immunity and cancer
David, C. J., & Massagué, J. (2018) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-018-0007-0 · Cited by 851
Growth inhibition by TGF-β linked to suppression of retinoblastoma protein phosphorylation.
Laiho, M., DeCaprio, J. A., Ludlow, J. W., Livingston, D. M., & Massague, J. (1990) · Cell · doi:10.1016/0092-8674(90)90251-9 · Cited by 797
Metadata
- Authors
- Roberts, A. B., Anzano, M. A., Wakefield, L. M., Roche, N. S., Stern, D. F., & Sporn, M. B.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 1985-01
- Volume
- 82
- Issue
- 1
- Pages
- 119-123
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W1992172901
- Cited by
- 1,094
- References
- 1
- FWCI
- 37.93
- Type
- journal article
- Language
- en
- Open access
- bronze
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- The paper
- Roberts, A. B., Anzano, M. A., Wakefield, L. M., Roche, N. S., Stern, D. F., & Sporn, M. B. (1985). Type beta transforming growth factor: a bifunctional regulator of cellular growth. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.82.1.119
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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