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TGF-β Signaling in Colon Cancer Cells

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Abstract

Transforming growth factor-betas (TGF-βs), cytokines expressed in the colon, play important roles as tumor suppressors and tumor promoters during colorectal carcinogenesis. TGF-β signaling pathway involves activation of Smad2 and Smad3 by the type I receptor and formation of Smad2/3/4 heteromeric complexes that enter the nucleus to regulate transcription. Most human colorectal cancers are resistant to the tumor suppressor effects of TGF-β, and a subset of human colorectal cancers have mutations in Smad2 and Smad4. The purpose of this study was to determine whether Smads are required for TGF-β signaling in colon cancer cells. First, we selected a colon cancer cell line (MC-26) that has a functional TGF-β signaling pathway. We found that MC-26 cells expressed Smad2, Smad3, and Smad4 mRNAs by reverse transeription-polymerase chain reaction and confirmed that the TGF-β signaling pathway is functional using a transient transfection assay with 3TP-Lux reporter plasmid. TGF-β also inhibited cell growth and induced apoptosis in MC-26 cells. When MC-26 cells were transiently transfected with dominant-negative carboxyl-terminal truncation mutants of Smad2, Smad3, and Smad4, TGF-β-induced 3TP-Lux reporter activity was significantly reduced, suggesting that Smad2, Smad3, and Smad4 are attractive novel therapeutic targets for regulating TGF-β signaling in colorectal cancers. Because MC-26 cells express TGF-β activated Smads, have a functional TGF-β signaling pathway, and are sensitive to the growth inhibitory and apoptotic effects of TGF-β, they can serve as an excellent model to examine TGF-β signaling in colorectal cancers.

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Acknowledgments

The authors thank Dr. D. Song for technical support and E. Figueroa and S. Schuenke for manuscript preparation. This work is supported by grants to T.C. Ko from the National Institutes of Health (RO1 DK060105 and PO1 DK35608) and a grant to C. M. Townsend, Jr. from the National Institutes of Health (PO1 DK35608).

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Authors and Affiliations

  1. Department of Surgery, The University of Texas Medical Branch, 301 University Boulevard, Galveston, Texas, 77555-0737, USA

    Fazhi Li M.D., Yanna Cao M.D., Courtney M. Townsend Jr. M.D. & Tien C. Ko M.D.

  2. Department of Human Biological Chemistry & Genetics, Sealy Center for Cancer Cell Biology, University of Texas Medical Branch, 301 University Boulevard, Galveston, Texas, 77555-0737, USA

    Tien C. Ko M.D.

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  1. Fazhi Li M.D.
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  2. Yanna Cao M.D.
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Correspondence to Tien C. Ko M.D..

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Li, F., Cao, Y., Townsend, C.M. et al. TGF-β Signaling in Colon Cancer Cells. World J. Surg. 29, 306–311 (2005). https://doi.org/10.1007/s00268-004-7813-6

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