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10 October 2002, Volume 21, Number 46, Pages 6983-6991
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Original Paper
Oncogenic transformation by bold beta-catenin: deletion analysis and characterization of selected target genes
Masahiro Aoki1, Vera Sobek1, Daniel J Maslyar1, Andreas Hecht2 and Peter K Vogt1

1Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, California, CA 92037, USA

2Institut fuer Molekulare Medizin und Zellforschung, Albert-Ludwigs-Universitaet Freiburg, Freiburg, Germany

Correspondence to: M Aoki, E-mail: maoki@scripps.edu

Abstract

Genetic analysis of beta-catenin-induced oncogenic transformation in chicken embryo fibroblasts (CEF) revealed the following prerequisites for oncogenicity: (1) removal of the N terminal phosphorylation sites targeted by glycogen synthase kinase 3beta (GSK3beta), (2) retention of the N terminal transactivation domain, and (3) retention of the armadillo repeats. The C terminal transactivation domain played an ancillary role in the transformation of CEF. There was a rough correlation between the transforming activity of various beta-catenin constructs and their transactivation of the TOPFLASH reporter. Expression levels of the candidate target genes of beta-catenin-LEF, cyclin D1 and myc were not correlated with each other or with the transforming activity of beta-catenin constructs. A new target gene, coding for inositol hexakisphosphate kinase 2 (IP6K2) was identified. Its expression showed concordance with the transforming activity of beta-catenin constructs.

Oncogene (2002) 21, 6983-6991. doi:10.1038/sj.onc.1205796

Keywords

beta-catenin; LEF/TCF; target genes; oncogenic transformation

Received 26 February 2002; revised 6 June 2002; accepted 18 June 2002
10 October 2002, Volume 21, Number 46, Pages 6983-6991
Table of contents    Previous  Abstract  Next   Full text  PDF
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