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Integrin-mediated signal transduction in transgenic mouse models of human breast cancer

The regulated growth and development of the mammary epithelium depends on the interaction between the epithelial cells with the adjacent extracellular matrix. This interaction is primarily mediated through the integrin receptor family. One of the primary signaling effectors on the integrin class of receptors is the integrin-linked kinase (ILK). To explore the importance of integrin coupled signaling pathways in mammary tumor progression, we have used transgenic mouse models to elucidate the role of the beta-1 integrin and ILK in mammary tumorigenesis and metastasis. First, we demonstrated that mammary epithelial expression of ILK is capable of inducing focal metastatic mammary tumors. Interestingly these mammary tumors exhibited evidence of epithelial mesenchymal transition. These observations provide direct evidence that mammary epithelial-specific expression of ILK can result in the direct induction of mammary tumors. To further explore the importance of the beta-1 class of integrin receptors and ILK in mammary tumorigenesis, we have generated mammary-specific knockouts of either beta-1 integrin or ILK using the Cre/LOXP recombination approach. Preliminary analyses of the mammary ductal outgrowth in these strains has revealed that a functional ILK is required for normal mammary gland development whereas a functional beta-1 integrin appears to be dispensable for normal mammary gland development. Although beta-1integrin receptor function is not required for normal mammary gland development, mammary-specific ablation of beta-1 results in dramatic inhibition of mammary tumors in transgenic mice expressing the Polyomavirus middle T oncogene. Taken together, these observations suggest that a functional beta-1 integrin receptor is required for efficient mammary tumor progression.

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White, D., Blaess, S., Mueller, U. et al. Integrin-mediated signal transduction in transgenic mouse models of human breast cancer. Breast Cancer Res 5 (Suppl 1), 4 (2003). https://doi.org/10.1186/bcr663

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  • DOI: https://doi.org/10.1186/bcr663

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