Autocrine Transforming Growth Factor β1 Modulates the Expression of Integrin α5β1 in Human Colon Carcinoma FET Cells
| Autor: | Lu Zhe Sun, DanHui Wang, Michael G. Brattain, Thomas M. Birkenmeier, Jiangen Gong, Guo-hao Zhou |
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| Rok vydání: | 1995 |
| Předmět: |
Integrins
biology Integrin Cell Biology Biochemistry Molecular biology CD49c Fibronectins Collagen receptor Cell biology Fibronectin Receptors Fibronectin Gene Expression Regulation Integrin alpha M Transforming Growth Factor beta Alpha-5 beta-1 Colonic Neoplasms Cell Adhesion Tumor Cells Cultured biology.protein Humans Integrin beta 6 RNA Messenger Autocrine signalling Molecular Biology |
| Zdroj: | Journal of Biological Chemistry. 270:14154-14159 |
| ISSN: | 0021-9258 |
| DOI: | 10.1074/jbc.270.23.14154 |
| Popis: | Transforming growth factor beta (TGF-beta) has been extensively studied as an exogenous agent that stimulates the expression of extracellular matrix proteins and their cell-surface integrin receptors in a variety of cell types. However, the recent demonstration of autocrine TGF-beta growth effects in a number of cell types suggests that the steady-state expression of extracellular matrix and integrin proteins and their biological activity may also be under autocrine TGF-beta control. Previously, we reported that repression of autocrine TGF-beta 1 activity by constitutive expression of a full-length TGF-beta 1 antisense cDNA led to abrogation of autocrine negative TGF-beta and, as a result, increased tumorigenicity and anchorage-independent growth of a poorly tumorigenic, well-differentiated colon carcinoma cell line designated FET (Wu, S., Theodorescu, D., Kerbel, R. S., Willson, J. K. V., Mulder, K. M., Humphrey, L. E., and Brattain, M. G. (1992) J. Cell Biol. 116, 187-196). Consequently, we have used this model system to study the effects of repression of autocrine TGF-beta 1 activity on the expression of integrin alpha 5 beta 1 and integrin alpha 5 beta 1-mediated cell adhesion to fibronectin. The expression of the integrin alpha 5 subunit was reduced in TGF-beta 1 antisense transfected FET cells at both mRNA and protein levels as determined by RNase protection assays and immunoprecipitation, respectively. Autocrine TGF-beta 1 had no effect on the transcription of integrin alpha 5 and beta 1 subunits, indicating that autocrine TGF-beta 1 may regulate integrin alpha 5 beta 1 expression at the post-transcriptional level. The diminished expression of integrin alpha 5 beta 1 on the cell surface led to the reduced adhesion of TGF-beta 1 antisense transfected cells to fibronectin. This phenomenon could be reversed by treatment with exogenous TGF-beta 1. |
| Databáze: | OpenAIRE |
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