A hypermorphic epithelial β-catenin mutation facilitates intestinal tumorigenesis in mice in response to compounding WNT-pathway mutations

M Buchert; F Rohde; M Eissmann; N Tebbutt; B Williams; CW Tan; A Owen; Y Hirokawa; A Gnann; G Orend; G Orner; RH Dashwood; JK Heath; M Ernst; KP Janssen

Journal article

A hypermorphic epithelial β-catenin mutation facilitates intestinal tumorigenesis in mice in response to compounding WNT-pathway mutations

M Buchert, F Rohde, M Eissmann, N Tebbutt, B Williams, CW Tan, A Owen, Y Hirokawa, A Gnann, G Orend, G Orner, RH Dashwood, JK Heath, M Ernst, KP Janssen

Dmm Disease Models and Mechanisms | COMPANY BIOLOGISTS LTD | Published : 2015

DOI: 10.1242/dmm.019844

Abstract

Activation of the Wnt/β-catenin pathway occurs in the vast majority of colorectal cancers. However, the outcome of the disease varies markedly from individual to individual, even within the same tumor stage. This heterogeneity is governed to a great extent by the genetic make-up of individual tumors and the combination of oncogenic mutations. In order to express throughout the intestinal epithelium a degradation-resistant β-catenin (Ctnnb1), which lacks the first 131 amino acids, we inserted an epitope-tagged ΔN(1-131)-β-cateninencoding cDNA as a knock-in transgene into the endogenous gpA33 gene locus in mice. The resulting gpA33ΔN-Bcat mice showed an increase in the constitutive Wnt/β-caten..

View full abstract

University of Melbourne Researchers

Niall Tebbutt Author

Chin Tan Author

Joan Heath Author

Related Projects (2)

COLORECTAL CANCER - MOLECULAR BASIS TO TARGETED THERAPEUTICS

Cancer of the colon and rectum is the most common form of cancer in Australia. Over 12,000 people are diagnosed each year with colorectal ca..

TARGETING COLON CANCER WITH JAK INHIBITORS

Colorectal cancer (CRC) is the 3rd most common cancer worldwide. 85% of CRC arises from mutations in the Wnt signalling pathway. We have sho..

Grants

Awarded by National Health and Medical Research Council

Funding Acknowledgements

The work in the laboratory of M.E. is supported by the Ludwig Institute for Cancer Research, the Victorian State Government Operational Infrastructure Support, the IRIISS scheme of the National Health and Medical Research Council Australia (NHMRC), and NHMRC grants #487922, #433617, #603122 and #1064987 (to M.B. and M.E.). M.E. is an NHMRC Senior Research Fellow. R.H.D. is supported by NIH P01 grant CA090890 and a Chancellor's Research Initiative from Texas A&M. Work in the laboratory of K.-P.J. is supported by grants from the Wilhelm Sander-Stiftung, the KKF (Kommission fuer klinische Forschung, Medical Faculty, TUM), and by a grant from DAAD/INCA Joint Translational Research Program on Cancer (to G. Orend. and K.-P. J.).