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Updated: Jun 22, 2026
Orthotopic Transplantation of Breast Tumors as Preclinical Models for Breast Cancer
Published on: May 18, 2020
Met induces diverse mammary carcinomas in mice and is associated with human basal breast cancer
Carrie R Graveel1, Jack D DeGroot, Yanli Su
1Department of Molecular Oncology, Van Andel Research Institute, Grand Rapids, MI 49503, USA.
Abstract:
Understanding the signaling pathways that drive aggressive breast cancers is critical to the development of effective therapeutics. The oncogene MET is associated with decreased survival in breast cancer, yet the role that MET plays in the various breast cancer subtypes is unclear. We describe a knockin mouse with mutationally activated Met (Met(mut)) that develops a high incidence of diverse mammary tumors with basal characteristics, including metaplasia, absence of progesterone receptor and ERBB2 expression, and expression of cytokeratin 5. With gene expression and tissue microarray analysis, we show that high MET expression in human breast cancers significantly correlated with estrogen receptor negative/ERBB2 negative tumors and with basal breast cancers. Few treatment options exist for breast cancers of the basal or trastuzumab-resistant ERBB2 subtypes. We conclude from these studies that MET may play a critical role in the development of the most aggressive breast cancers and may be a rational therapeutic target.
Insights
The oncogene MET drives aggressive basal breast cancers. Targeting MET may offer new treatment options for estrogen receptor-negative and ERBB2-negative breast tumors.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Aggressive breast cancers require novel therapeutic targets.
- The oncogene MET is linked to reduced survival but its role across breast cancer subtypes is not fully understood.
Purpose of the Study:
- To investigate the role of the oncogene MET in aggressive breast cancer development and subtypes.
- To determine if MET is a potential therapeutic target for difficult-to-treat breast cancers.
Main Methods:
- Generated a knockin mouse model with a mutationally activated Met (Met(mut)) oncogene.
- Analyzed mammary tumor characteristics in the mouse model.
- Utilized gene expression and tissue microarray analysis on human breast cancer samples.
Main Results:
- Met(mut) mice developed diverse mammary tumors with basal characteristics.
- High MET expression in human breast cancers correlated significantly with estrogen receptor-negative/ERBB2-negative and basal subtypes.
- Basal and trastuzumab-resistant ERBB2 subtypes have limited treatment options.
Conclusions:
- The oncogene MET plays a critical role in the pathogenesis of aggressive breast cancers.
- MET represents a rational therapeutic target for aggressive, basal, and ERBB2-negative breast cancers.
