TGF-β inhibits Akt-induced transformation in intestinal epithelial cells

Yanna Cao, Chunyan Deng, Courtney Townsend, Tien C. Ko

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Background: During the early stages of colorectal carcinogenesis, the phosphatidylinositol 3-kinase (PI3K)/Akt pathway is activated, enabling the transformed cells to survive and grow in the absence of anchorage to extracellular matrix. Transforming growth factor β (TGF-β) is an important tumor suppressor in the colon, and it is inactivated during later stages of colorectal carcinogenesis. The purpose of this study was to determine whether TGF-β inhibits Akt-induced anchorage-independent growth and resistance to anoikis in gut epithelial cells. Methods: Rat intestinal epithelial cells (RIE-1) were infected with a retrovirus containing pLXSN-mAkt, and three independent clones were selected. Anchorage-independent growth was examined by colony formation in soft agar and cell counting in ultralow attachment plates. Anoikis was analyzed with the use of Annexin V staining. Results: All three clones of RIE-1/mAkt formed colonies in soft agar, which were decreased by TGF-β. TGF-β induced anoikis and treatment with a general caspase inhibitor, zVAD-fluoromethyl ketone, blocked TGF-β-mediated decrease in colony formation. Conclusions: TGF-β attenuated Akt-induced anchorage-independent growth in RIE-1 cells in part by enhancing anoikis. Our data demonstrate a novel tumor-suppressor activity of TGF-β and provide the molecular justification for the required activation of the PI3K/Akt pathway and the subsequent inactivation of TGF-β signaling during colorectal carcinogenesis.

Original languageEnglish (US)
Pages (from-to)322-329
Number of pages8
JournalSurgery
Volume140
Issue number2
DOIs
StatePublished - Aug 2006

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Transforming Growth Factors
Epithelial Cells
Anoikis
Phosphatidylinositol 3-Kinase
Carcinogenesis
Agar
Growth
Clone Cells
Caspase Inhibitors
Annexin A5
Retroviridae
Ketones
Extracellular Matrix
Neoplasms
Colon
Staining and Labeling

ASJC Scopus subject areas

  • Surgery

Cite this

TGF-β inhibits Akt-induced transformation in intestinal epithelial cells. / Cao, Yanna; Deng, Chunyan; Townsend, Courtney; Ko, Tien C.

In: Surgery, Vol. 140, No. 2, 08.2006, p. 322-329.

Research output: Contribution to journalArticle

Cao, Yanna ; Deng, Chunyan ; Townsend, Courtney ; Ko, Tien C. / TGF-β inhibits Akt-induced transformation in intestinal epithelial cells. In: Surgery. 2006 ; Vol. 140, No. 2. pp. 322-329.
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