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Bin1 ablation in mammary gland delays tissue remodeling and drives cancer progression.

Cancer research | Jan 1, 2007

http://www.ncbi.nlm.nih.gov/pubmed/17210688

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.

Pubmed ID: 17210688 RIS Download

Mesh terms: 9,10-Dimethyl-1,2-benzanthracene | Adaptor Proteins, Signal Transducing | Animals | Base Sequence | Carcinogens | Cell Transformation, Neoplastic | Cocarcinogenesis | Disease Progression | Female | Gene Deletion | Genes, ras | Mammary Glands, Animal | Mammary Neoplasms, Experimental | Mice | Mice, Transgenic | Molecular Sequence Data | Nerve Tissue Proteins | Pregnancy | Tumor Suppressor Proteins

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Associated grants

  • Agency: NCI NIH HHS, Id: CA 100123
  • Agency: NCI NIH HHS, Id: R01 CA100123

Mouse Genome Informatics (Data, Gene Annotation)

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