The Role of the Integrin-Linked Kinase (ILK) in Mammary Gland Tumorigenesis and Metastasis
Annual rept, 15 Jun 1999-15 Jun 2000
MCMASTER UNIV HAMILTON (ONTARIO)
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The primary objective of this proposal is to elucidate the role of the integrin linked kinase in the induction of mammary tumors. To accomplish this, we have generated transgenic mice that express a cDNA encoding ILK under the transcriptional control of the mouse mammary tumor virus MMTV promoter enhancer. Although mammary epithelial expression of ILK was capable of inducing mammary tumors in female transgenic mice, these tumors were focal in nature and arose with a long latency period. Tumor progression in these strains involved a dramatic upregulation in both the levels of ILK and cycling Dl protein. In addition, constitutive phosphorylation of AKt on serine 473 was also observed in both normal and tumor material . These observations suggest that ILK is capable of inducing tumors through the concerted activation of multiple distinct signaling pathways. We have also recently derived transgenic mice that express a kinase defective ILK under the MMTV promoter. Future crosses with both types of ILK strains with other oncogene bearing transgenic strains will provide important insight into the role of ILK in mammary tumorigenesis and metastasis.
- Medicine and Medical Research