NOTE TO USERS This reproduction is the best copy available. UMI THE ROLE OF PI-INTEGRIN RECEPTOR SIGNALING IN MAMMARY GLAND

ii Experimental and clinical evidence implicate the ~l-integrin subunit and its associated intracellular effector ILK in the initiation and progression of human breast cancer. Roles for these proteins in promoting the oncogenic process, however, have not been demonstrated in vivo. As a result, experiments were designed to test the tumour-promoting properties of~l-integrin and ILK in the mammary glands of transgenic mice. The first of these experiments involved the targeted ablation of a conditional allele of ~l-integrin in a transgenic mouse model of human breast cancer. Using this approach, it was found that the expression of ~l-integrin is required for oncogene-induced transformation of the mammary gland epithelium in vivo. This requirement for ~ l-integrin expression was observed during both the initiation of tumourigenesis, as well as for maintaining the growth of established tumours. In addition, a block in tumour cell proliferation following ablation of P l-integrin expression was found to be associated with the suppression of F AK autophosphorylation, providing a molecular mechanis