RUNX3 inhibits cell proliferation and induces apoptosis by reinstating transforming growth factor beta responsiveness in esophageal adenocarcinoma cells

Alfonso Torquati, Lynda O'Rear, Lara Longobardi, Anna Spagnoli, William O. Richards, R. Daniel Beauchamp

Research output: Contribution to journalArticle

46 Scopus citations

Abstract

Background SEG-1, a Barrett's-derived esophageal adenocarcinoma cell line, is not responsive to transforming growth factor beta (TGF-β) growth effects. We hypothesize that SEG-1 cells lack the tumor-suppressor gene Runt domain transcription factor 3 (RUNX3) and that its reinstatement can restore the antiproliferative and apoptotic effects of TGF-β. Methods RUNX3 expression was assessed by immunoblotting. SEG-1 cells were transfected with RUNX3 and treated with TGF-β. The effects of RUNX3 transfection on cell proliferation and apoptosis were determined. Smad-mediated TGF-β transcriptional activity was evaluated with the use of dual-luciferase assay. Results SEG-1 cells are not responsive to TGF-β. SEG-1 cells lack RUNX3 protein expression, while RUNX3 is highly expressed in normal human gastric and esophageal epithelium. Although the Smad-2 signaling is activated by TGF-β, SEG-1 cells lack Smad-mediated TGF-β transcriptional activity. In cells transfected with RUNX3, TGF-β acquired an antiproliferative effect and induced apoptosis (P=.001). RUNX3 transfection, in the absence of TGF-β, had no effect on proliferation and apoptosis of SEG-1 cells. RUNX3 expression dramatically increases SMAD-mediated TGF-β-induced transcriptional activity when compared with controls (P=.0001). Conclusions RUNX3 is not expressed in SEG-1 cells, while it is present in normal esophageal mucosa. RUNX3 is essential for the antiproliferative and apoptotic effects of TGF-β in SEG-1 cells and for the Smad-mediated transcriptional activity of TGF-β.

Original languageEnglish (US)
Pages (from-to)310-316
Number of pages7
JournalSurgery
Volume136
Issue number2
DOIs
StatePublished - Aug 2004

ASJC Scopus subject areas

  • Surgery

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