The PEA3 Subfamily of Ets Transcription Factors Synergizes with β-Catenin–LEF-1 To Activate Matrilysin Transcription in Intestinal Tumors

• DOI: 10.1128/mcb.21.4.1370-1383.2001
• Publication Date: 2002-07-27T10:06:23Z
• Authors: Howard C. Crawford; Barbara Fingleton; Mark D. Gustavson; Natasza Kurpios; Rebecca A. Wagenaar; John A. Hassell; Lynn M. Matrisian
• Keywords: Matrilysin; Subfamily; Transcription

The matrix metalloproteinase matrilysin (MMP-7) is expressed in the tumor cells of a majority mouse intestinal and human colonic adenomas.We showed previously that target gene ␤-catenin-Tcf, transcription factor complex whose activity thought to play crucial role initiation tumorigenesis.Here we report overexpression stable mutant form ␤-catenin alone was not sufficient effect expression luciferase from promoter-luciferase reporter plasmid.However, cotransfection with an vector encoding PEA3 Ets factor, or its close relatives ER81 ERM, increased rendered promoter responsive ␤-catenin-LEF-1 as well AP-1 protein c-Jun.Other proteins could substitute for subfamily.Luciferase induced up 250-fold when PEA3, c-Jun, ␤-catenin, LEF-1 were coexpressed.This combination factors also induce endogenous gene.Furthermore, all matrilysin-expressing benign tumors Min member subfamily, did colon cell lines examined.These data suggest members conjunction accumulation these tumors, leads coordinate upregulation transcription, contributing gastrointestinal tumorigenesis.