The Role of the Integrin-Linked Kinase (ILK) in Mammary Gland Tumorigenesis and Metastasis
Annual summary rept. 1 May 2000-1 May 2001
MCMASTER UNIV HAMILTON (ONTARIO)
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The research objective outlined in the original proposal was to determine the role of the integrin-linked kinase ILK in the induction and progression of mammary tumors. This work was initially based on the observation that overexpression of ILK in cultured epithelial cells results in changes characteristic of oncogenic transformation Hannigan et al., 1996. In order to evaluate the oncogenic potential of ILK in the mammary gland, we derived transgenic mice expressing ILK under the transcriptional control of the MMTV promoter. The appearance of mammary tumors in these MMTVILK mice confirmed that mammary-specific overexpression of ILK can facilitate malignant transformation in vivo. This result provides the first direct demonstration of an oncogenic role for ILK, which may have significance to the clinical management of breast cancer, given that ILK protein levels are elevated in human tumors and tumor cell lines Chung et al., 1998 Janji et al., 1999. The results of the experiment were submitted as a manuscript to the journal Oncogene. In addition to this main research objective, we have also shown that mammary-specific expression of a kinase-dead allele of ILK does not inhibit erbB-2-mediated tumorigenesis, suggesting the importance of ILK protein adaptor functions, retained in the kinase-dead allele.
- Anatomy and Physiology
- Medicine and Medical Research