The Role of Cyclin Dependent Kinase Inhibitor, CIP1, in Breast Cancer.
Annual rept. 15 Sep 96-14 Sep 97
BAYLOR COLL OF MEDICINE HOUSTON TX
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Breast cancer results from inappropriate cell proliferation due to mutations that disrupt normal cell cycle control. Our studies are focused on understanding the role of the p21 Cip 1 protein in cancer. p21 is a member of a growing family of proteins which bind and inhibit cyclin dependent kinases Cdks. Cdks are required for cell cycle progression. p21 is regulated by the tumor suppressor protein p53 and is thought to contribute to p53s tumor suppressor function through its interaction with Cdks. p53 is commonly mutated in breast cancer. We have examined the expression of p21 during development and in adult tissues and have found that p21 expression is highly selective and correlates with terminal differentiation. We have also analyzed the phenotype of mice lacking p21. We have found that p21 is responsible for only a subset of p53s function. Specifically, p21 is required for G1 checkpoint function but is not required for the G2 checkpoint or apoptosis induction. Moreover, animals lacking p21 do not readily develop tumors, implying that p21 is not a tumor suppressor. Additional studies have led to a further understanding of the regulation of p21 and the identity of its targets.
- Anatomy and Physiology