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

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

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

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

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

Correspondence to: W J Muller, MOBIX, McMaster University, 1280 Main Street West, Hamilton, Ontario, Canada L8S 4K1; E-mail: mullerw@mcmaster.ca

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-3. 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-3 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. Oncogene (2001) 20, 7064-7072.

integrin linked kinase; ILK; transgenic mice; mammary epithelium; breast cancer; tumorigenesis