The Role of Cyclin Dependent Kinase Inhibitor, CIP1, in Breast Cancer.

The cell cycle is regulated by the action of a family of cyclin dependent kinases Cdks which catalyze particular cell cycle transitions. Cdks arc positively regulated through interaction with cyclins and are negatively regulated through phosphorylation and through association with inhibitory proteins of the CIPKIP and INK4 families. We initially identified p21CIP1 as an inhibitor of the 61S kinases Cdk2. Since that time, we and others have identified additional p21CIP1 homologs inducing p27KIP1 and p57KIP2. Our research has focused on the role of p21CIP1 in development and cancer. We have found that p21CIP1 is expressed in a highly cell type specific manner during embryonic development and in adult tissues, being most highly expressed in terminally differentiated cells. Through analysis of p21 deficient mice, however, we have found that p21CIP1 is not required for normal development but fibroblast from p21 deficient mice have a defect in the 61 DNA damage checkpoint regulated by p53, indicating that tumor suppression by p53 is complex. Current studies are aimed at understanding in greater detail the function of p21 and its possible role in human cancers.