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Alterations in Cell Cycle Regulatory Genes in Breast Cancer

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Breast Cancer in the Post-Genomic Era

Part of the book series: Current Clinical Oncology ((CCO))

Summary

Breast cancer is one of the most commonly diagnosed cancers worldwide. The underlying mechanisms accountable for aberrant cell proliferation and tumor growth involve multiple pathways, which include components of the cell cycle machinery. Proto-oncogene activation, loss of tumor suppressor genes, and growth sustained by growth factors and steroids may affect breast cancer initiation and progression. The regulation of cell cycle checkpoints is critical for the proper and orchestrated transition from one phase of the cell cycle to the next. The deregulation of these checkpoints plays a key role in the transformation process, allowing the cells to continuously cycle under conditions inadequate for normal cell proliferation. A key regulatory pathway determining cell cycle proliferation rate is the cyclin/cyclin-dependent kinase (CDK)/p16Ink4A/retinoblastoma protein (pRb) axis. Alterations affecting components of this pathway through overexpression, mutation, and epigenetic gene silencing are almost universal in human cancer. In breast cancer, these include the overexpression of cyclins D1 and cyclin E, decreased expression of the p27Kip1 CDK inhibitor, and silencing of the p16 Ink4A gene through promoter methylation. Understanding the biology of breast cancer may improve the possibility to overcome this pathology. The chance to have strong prognostic and/or predictive markers will be an immensely useful tool to identify patients at higher risk of relapse and to select the most appropriate systemic treatment for individual breast cancer patients.

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  1. Sbarro Institute for Cancer Research and Molecular Medicine, Center for Biotechnology College of Science and Technology, Temple University, Philadelphia, PA, 19122, USA

    Annalisa Roberti, Marcella Macaluso & Antonio Giordano MD

  2. Department of Human Pathology and Oncology, University of Siena, 53100, Siena, Italy

    Annalisa Roberti, Marcella Macaluso & Antonio Giordano MD

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  1. Annalisa Roberti
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    © 2009 Humana Press, a part of Springer Science+Business Media, LLC

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    Roberti, A., Macaluso, M., Giordano, A. (2009). Alterations in Cell Cycle Regulatory Genes in Breast Cancer. In: Giordano, A., Normanno, N. (eds) Breast Cancer in the Post-Genomic Era. Current Clinical Oncology. Humana Press. https://doi.org/10.1007/978-1-60327-945-1_4

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