Original Article

Oncogene (2012) 31, 3298–3309; doi:10.1038/onc.2011.486; published online 24 October 2011

Transgenic IGF-IR overexpression induces mammary tumors with basal-like characteristics, whereas IGF-IR-independent mammary tumors express a claudin-low gene signature
Open

S E Franks1,3, C I Campbell1,3, E F Barnett1,3, M D Siwicky1,3, J Livingstone2, S Cory2 and R A Moorehead1

  1. 1Department of Biomedical Sciences, Ontario Veterinary College, University of Guelph, Guelph, Ontario, Canada
  2. 2Departments of Biochemistry Oncology and Medicine, Rosalind and Morris Goodman Cancer Research Centre, McGill University, Montreal, Quebec, Canada

Correspondence: Dr RA Moorehead, Department of Biomedical Sciences, Ontario Veterinary College, University of Guelph, 50 Stone Road East, Guelph, Ontario, Canada N5A7Z1. E-mail: rmoorehe@uoguelph.ca

3These authors contributed equally to this work.

Received 6 March 2011; Revised 18 September 2011; Accepted 18 September 2011
Advance online publication 24 October 2011

Top

Abstract

Molecular profiling has allowed a more precise classification of human cancers. With respect to breast cancer, this approach has been used to identify five subtypes; luminal A, luminal B, HER2-enriched, basal-like and claudin-low. In addition, this approach can be used to determine the type of tumor represented by particular cell lines or transgenic animal models. Therefore, this approach was utilized to classify the mammary tumors that develop in MTB-IGFIR transgenic mice. It was determined that the primary mammary tumors, which develop due to elevated expression of the type I insulin-like growth factor receptor (IGF-IR) in mammary epithelial cells, most closely resemble murine tumors with basal-like or mixed gene expression profiles and with human basal-like breast cancers. Downregulation of IGF-IR transgene in MTB-IGFIR tumor-bearing mice leads to the regression of most of the tumors, followed by tumor reappearance in some of the mice. These tumors that reappear following IGF-IR transgene downregulation do not express the IGF-IR transgene and cluster with murine mammary tumors that express a mesenchymal gene expression profile and with human claudin-low breast cancers. Therefore, IGF-IR overexpression in murine mammary epithelial cells induces mammary tumors with primarily basal-like characteristics, whereas tumors that develop following IGF-IR downregulation express a gene signature that most closely resembles human claudin-low breast tumors.

Keywords:

IGF-IR; mammary tumor; DNA microarray; EMT; claudin