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Mammary epithelial-specific expression of the integrin linked kinase (ILK) results in the induction of mammary gland hyperplasias and tumors in transgenic mice

Oncogene volume 20, pages 7064–7072 (2001)Cite this article

Abstract

The integrin linked kinase (ILK) is a cytoplasmic effector of integrin receptors, involved in the regulation of integrin binding properties as well as the activation of cell survival and proliferative pathways, including those involving MAP kinase, PKB/Akt and GSK-3β. Overexpression of ILK in cultured intestinal and mammary epithelial cells has been previously shown to induce changes characteristic of oncogenic transformation, including anchorage-independent growth, invasiveness, suppression of anoikis and tumorigenicity in nude mice. In order to determine if ILK overexpression can result in the formation of mammary tumors in vivo, we generated transgenic mice expressing ILK in the mammary epithelium, under the transcriptional control of the mouse mammary tumor virus (MMTV) long terminal repeat (LTR). By the age of 6 months, female MMTV/ILK mice developed a hyperplastic mammary phenotype, which was accompanied by the constitutive phosphorylation of PKB/Akt, GSK-3β and MAP kinase. Focal mammary tumors subsequently appeared in 34% of the animals at an average age of 18 months. Given the focal nature and long latency of the tumors, however, additional genetic events are likely required for tumor induction in the MMTV/ILK mice. These results provide the first direct demonstration of a potential oncogenic role for ILK, which is upregulated in human tumors and tumor cell lines.

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Acknowledgements

The authors would like to thank Judy E Walls (UC Davis School of Medicine) for excellent technical work on the immunohistochemistry, and Monica Graham (McMaster University) for genotyping the ILK strains. This work was supported by the US Department of Defense Breast Cancer Research Initiative DAMD 17-99-1-9284 (D White) and DAMD 17-99-1-9286 (WJ Muller), by grants from the National Cancer Institute of Canada (S Dedhar), and by grant 5JB-0014 from the State of California Breast Cancer Research Program (RD Cardiff).

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Authors and Affiliations

  1. MOBIX and Department of Medical Sciences, McMaster University, Hamilton, Canada, L8S 4K1, Ontario

    Donald E White

  2. Center for Comparative Medicine, University of California at Davis, Davis, CA 95616, California, USA

    Robert D Cardiff

  3. British Columbia Cancer Agency, Jack Bell Research Centre, Vancouver, V6H 3Z6, British Columbia, Canada

    Shoukat Dedhar

  4. Department of Biochemistry and Molecular Biology, University of British Columbia, Vancouver, V6H 3Z6, British Columbia, Canada

    Shoukat Dedhar

  5. MOBIX and Department of Pathology and Molecular Medicine, McMaster University, Hamilton, L8S 4K1, Ontario, Canada

    William J Muller

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  1. Donald E White
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Correspondence to William J Muller.

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White, D., Cardiff, R., Dedhar, S. et al. Mammary epithelial-specific expression of the integrin linked kinase (ILK) results in the induction of mammary gland hyperplasias and tumors in transgenic mice. Oncogene 20, 7064–7072 (2001). https://doi.org/10.1038/sj.onc.1204910

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