TGF-β signaling in colon cancer cells

Fazhi Li, Yanna Cao, Courtney Townsend, Tien C. Ko

Research output: Contribution to journalArticle

41 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)306-311
Number of pages6
JournalWorld Journal of Surgery
Volume29
Issue number3
DOIs
StatePublished - Mar 2005

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Colonic Neoplasms
Colorectal Neoplasms
Growth
Transforming Growth Factor beta
Carcinogens
Transfection
Neoplasms
Colon
Carcinogenesis
Plasmids
Apoptosis
Cytokines
Cell Line
Polymerase Chain Reaction
Messenger RNA
Mutation

ASJC Scopus subject areas

  • Surgery

Cite this

TGF-β signaling in colon cancer cells. / Li, Fazhi; Cao, Yanna; Townsend, Courtney; Ko, Tien C.

In: World Journal of Surgery, Vol. 29, No. 3, 03.2005, p. 306-311.

Research output: Contribution to journalArticle

Li, Fazhi ; Cao, Yanna ; Townsend, Courtney ; Ko, Tien C. / TGF-β signaling in colon cancer cells. In: World Journal of Surgery. 2005 ; Vol. 29, No. 3. pp. 306-311.
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