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Updated: Jul 17, 2026
Modeling Breast Cancer via an Intraductal Injection of Cre-expressing Adenovirus into the Mouse Mammary Gland
Published on: June 7, 2019
Bin1 ablation in mammary gland delays tissue remodeling and drives cancer progression
Mee Young Chang1, Janette Boulden, Erika Sutanto-Ward
1Lankenau Institute for Medical Research, 100 Lancaster Avenue, Wynnewood, PA 19096, USA.
Abstract:
Genes that modify oncogenesis may influence dormancy versus progression in cancer, thereby affecting clinical outcomes. The Bin1 gene encodes a nucleocytosolic adapter protein that interacts with and suppresses the cell transforming activity of Myc. Bin1 is often attenuated in breast cancer but its ability to negatively modify oncogenesis or progression in this context has not been gauged directly. In this study, we investigated the effects of mammary gland-specific deletion of Bin1 on initiation and progression of breast cancer in mice. Bin1 loss delayed the outgrowth and involution of the glandular ductal network during pregnancy but had no effect on tumor susceptibility. In contrast, in mice where tumors were initiated by the ras-activating carcinogen 7,12-dimethylbenz(a)anthracene, Bin1 loss strongly accentuated the formation of poorly differentiated tumors characterized by increased proliferation, survival, and motility. This effect was specific as Bin1 loss did not accentuate progression of tumors initiated by an overexpressed mouse mammary tumor virus-c-myc transgene, which on its own produced poorly differentiated and aggressive tumors. These findings suggest that Bin1 loss cooperates with ras activation to drive progression, establishing a role for Bin1 as a negative modifier of oncogenicity and progression in breast cancer.
Insights
Loss of the Bin1 gene in mice accelerates breast cancer progression, particularly when combined with ras activation. This suggests Bin1 acts as a tumor suppressor, impacting cancer development and clinical outcomes.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Genes influencing oncogenesis can dictate cancer dormancy or progression.
- The Bin1 gene, a nucleocytosolic adapter protein, suppresses Myc's transforming activity.
- Bin1 is frequently reduced in breast cancer, but its direct role in modifying oncogenesis is unclear.
Purpose of the Study:
- To investigate the impact of mammary gland-specific Bin1 deletion on breast cancer initiation and progression in mice.
- To determine if Bin1 loss affects tumor susceptibility or aggressiveness.
Main Methods:
- Mammary gland-specific deletion of the Bin1 gene in mice.
- Initiation of breast cancer using the ras-activating carcinogen 7,12-dimethylbenz(a)anthracene.
- Comparison with tumors initiated by an overexpressed mouse mammary tumor virus-c-myc transgene.
Main Results:
- Bin1 loss delayed mammary gland development during pregnancy but did not affect initial tumor susceptibility.
- In ras-activated tumors, Bin1 loss significantly enhanced the formation of poorly differentiated tumors with increased proliferation, survival, and motility.
- Bin1 loss did not worsen progression in tumors initiated by c-myc overexpression.
Conclusions:
- Bin1 loss cooperates with ras activation to drive breast cancer progression.
- Bin1 functions as a negative modifier of oncogenicity and progression in breast cancer.
- These findings highlight Bin1's role in modulating aggressive tumor phenotypes.
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