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Oncogenic transformation by β-catenin: deletion analysis and characterization of selected target genes

Abstract

Genetic analysis of β-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 3β (GSK3β), (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 β-catenin constructs and their transactivation of the TOPFLASH reporter. Expression levels of the candidate target genes of β-catenin-LEF, cyclin D1 and myc were not correlated with each other or with the transforming activity of β-catenin constructs. A new target gene, coding for inositol hexakisphosphate kinase 2 (IP6K2) was identified. Its expression showed concordance with the transforming activity of β-catenin constructs.

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Acknowledgements

This work was supported by NIH research grants CA 79616 and CA 78230. This is manuscript number 14600-MEM of the Department of Molecular and Experimental Medicine, The Scripps Research Institute.

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Correspondence to Masahiro Aoki.

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Aoki, M., Sobek, V., Maslyar, D. et al. Oncogenic transformation by β-catenin: deletion analysis and characterization of selected target genes. Oncogene 21, 6983–6991 (2002). https://doi.org/10.1038/sj.onc.1205796

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