Centrosome Defects, Genetic Instability and Breast Cancer Progression
Annual summary rept. 21 Jul 2003-20 Jul 2004
MASSACHUSETTS UNIV MEDICAL CENTER WORCESTER
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Breast cancer is the most prevalent of all cancers and it is the second cause of cancer death among women. Centrosome defects have been implicated in cancer formation and we showed that they can be detected very early on in this process, in the precancerous lesions. The centrosome protein, pericentrin, is overexpressed in many types of tumors including breast, and in this study we tried to understand the role of pericentrin in carcinogenesis. We found that pericentrin down regulation by RNA interference causes cytokinesis defects which can contribute to aneuploidy and thus cancer formation. We also identified a centrosome damage G0G1 checkpoint that is dependent upon intact p53 and p38 signaling. Moreover, we showed that pericentrin down regulation is involved in the differentiation process through inhibition of ciliogenesis. Uncontrollable cell division in cells that should otherwise be in a differentiated state is the very first step in cancer formation. Better understanding of all of these processes is necessary for implementing a better treatment for breast cancer in order to reduce the mortality rates associated with this deadly disease.
- Anatomy and Physiology
- Medicine and Medical Research