grantor:
University of TorontoOverexpression of ILK in rat epithelial cells results in decreased cell adhesion and anchorage-independent growth. I hypothesized, therefore, that overexpression of ILK would directly or indirectly affect the cell cycle machinery. Cell adhesion to substratum has been shown to regulate cyclin A expression as well as cyclin D and E-dependent kinases. Here, I demonstrate that stable transfection and overexpression of the Integrin Linked Kinase (ILK) induces anchorage-independent cell cycle progression but not serum-independent growth of IEC18 rat intestinal epithelial cells. ILK overexpression results in increased expression of cyclin D1 and cyclin A, activation of cdk4 and cyclin E-associated kinases, and hyperphosphorylation of the retinoblastoma protein. In addition, p21 and p27 cdk inhibitors display altered electrophoretic mobilities, with p27 having reduced inhibitory activity. These results indicate that, when overexpressed, ILK induces signalling pathways resulting in the stimulation of G1/S cyclin-cdk activities which are normally regulated by cell adhesion and integrin engagement.M.Sc
