Cyclin E and Cks proteins are frequently overexpressed in a broad spectrum of human cancers, and as we have shown for breast cancer, often in the same tumors. Yet, how these proteins contribute to oncogenesis is poorly understood. Compounding the problem of understanding their roles in oncogenesis is an incomplete delineation of their basic biological functions. In this proposal we aim to address both of these issues. We will use a combination of biochemical, cell based and animal based approaches in the hope of providing a comprehensive picture of how these proteins function individually and in concert during the cell cycle and in oncogenesis.
Cancer is a disease with tremendous health implications for the US and world, and yet, only limited progress has been made in curing most types of cancer. In part, this is because many mechanistic questions concerning the basic biology of cancer remain unanswered. This proposal seeks to address some of these unanswered questions.
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|Best, D Hunter; Coleman, William B (2007) Treatment with 2-AAF blocks the small hepatocyte-like progenitor cell response in retrorsine-exposed rats. J Hepatol 46:1055-63|
|Best, D Hunter; Coleman, William B (2007) Bile duct destruction by 4,4'-diaminodiphenylmethane does not block the small hepatocyte-like progenitor cell response in retrorsine-exposed rats. Hepatology 46:1611-9|
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|Smith, A P L; Henze, M; Lee, J A et al. (2006) Deregulated cyclin E promotes p53 loss of heterozygosity and tumorigenesis in the mouse mammary gland. Oncogene 25:7245-59|
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