Transforming growth factor beta (TGF-beta) exerts an inhibitory effect on the growth of most epithelial cell types, and the loss of responsiveness to this growth inhibition has been implicated in the development of a variety of human cancers. The genetic alteration of TGF-beta receptors is known to
Clonal heterogeneity of the sensitivity of human colon carcinoma cell lines to TGFβ isoforms
✍ Scribed by Guo-Hao K. Zhou; Gwendolyn L. Sechrist; Michael G. Brattain; Kathleen M. Mulder
- Publisher
- John Wiley and Sons
- Year
- 1995
- Tongue
- English
- Weight
- 907 KB
- Volume
- 165
- Category
- Article
- ISSN
- 0021-9541
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✦ Synopsis
Abstract
Spontaneously arising, TGFβ~1~‐resistant colonies were isolated directly from the soft agarose plates of MOSER human colon carcinoma cells grown in the presence of TGFβ~1~ but in the absence of serum. The colonies were cloned by limiting dilution and screened in a monolayer proliferation assay for sensitivity to TGFβ~1~ and TGFβ~2~ isoforms. Cell clones selectively sensitive or resistant to these isoforms in the growth inhibition assay displayed similar differential sensitivities to TGFβ isoforms for production of the extracellular matrix proteins laminin and fibronectin, as well as for the expression of the colon cell differentiation marker carcinoembryonic antigen. Differential receptor binding profiles for TGFβ~1~ and TGFβ~2~ were observed among the clones. The isolation of cell clones selectively resistant or sensitive to TGFβ isoforms as well as the identification of differential receptor binding profiles among the clones indicate the heterogeneity of TGFβ responsiveness that exists naturally in human colon tumor cells and stress the importance of defining mechanisms underlying differential responsiveness to TGFβ isoforms. © 1995 Wiley‐Liss Inc.
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