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Molecular Cancer
Published in: Molecular Cancer 1/2010

Open Access 01-12-2010 | Research

ErbB2 enhances mammary tumorigenesis, oncogene-independent recurrence and metastasis in a model of IGF-IR-mediated mammary tumorigenesis

Authors: Craig I Campbell, James J Petrik, Roger A Moorehead

Published in: Molecular Cancer | Issue 1/2010

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Abstract

Background

The type I insulin-like growth factor receptor (IGF-IR) and ErbB2 (Her-2) are receptor tyrosine kinases implicated in human breast cancer. Both proteins are currently the subject of targeted therapeutics that are used in the treatment of breast cancer or which are in clinical trials. The focus of this study was to utilize our inducible model of IGF-IR overexpression to explore the interaction of these two potent oncogenes.

Results

ErbB2 was overexpressed in our RM11A cell line, a murine tumor cell line that overexpresses human IGF-IR in an inducible manner. ErbB2 conferred an accelerated tumor onset and increased tumor incidence after injection of RM11A cells into the mammary glands of syngeneic wild type mice. This was associated with increased proliferation immediately after tumor cell colonization of the mammary gland; however, this effect was lost after tumor establishment. ErbB2 overexpression also impaired the regression of established RM11A tumors following IGF-IR downregulation and enhanced their metastatic potential.

Conclusion

This study has revealed that even in the presence of vast IGF-IR overexpression, a modest increase in ErbB2 can augment tumor establishment in vivo, mediate resistance to IGF-IR downregulation and facilitate metastasis. This supports the growing evidence suggesting a possible advantage of using IGF-IR and ErbB2-directed therapies concurrently in the treatment of breast cancer.
Appendix
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Metadata
Title
ErbB2 enhances mammary tumorigenesis, oncogene-independent recurrence and metastasis in a model of IGF-IR-mediated mammary tumorigenesis
Authors
Craig I Campbell
James J Petrik
Roger A Moorehead
Publication date
01-12-2010
Publisher
BioMed Central
Published in
Molecular Cancer / Issue 1/2010
Electronic ISSN: 1476-4598
DOI
https://doi.org/10.1186/1476-4598-9-235

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