Cellular Consequences of Telomere Shortening in Histologically Normal Breast Tissues
Annual summary rept. 1 Sep 2009-31 Aug 2010
JOHNS HOPKINS UNIV BALTIMORE MD
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We recently demonstrated that telomere lengths were shorter in more aggressive breast cancer subtypes, such as luminal B, HER-2 positive and triple-negative tumors, suggesting tumor telomere length may have clinical utility as a prognostic andor risk marker for breast cancer. Interestingly, the investigator has shown that moderate telomere shortening occurs specifically in luminal epithelial cells, but not in myoepithelial cells, in the majority of histologically normal terminal ductal lobular units analyzed from patients undergoing reduction mammoplasty, but the extent and degree of shortening varies by the individual. These data imply that there is a reservoir of genetically altered, yet histologically normal, cells within normal breast tissues that may represent fertile ground for tumor development. Since telomere shortening has been associated with cellular senescence and dysfunctional telomeres have been linked to the DNA damage response pathway in cancerous tissues, future planned experiments will assess senescence-associated markers and DNA damage response pathway markers in histologically normal human breast tissues that display either normal or short telomeres i.e. prior to tumor formation. In addition, the proposed investigation has provided grounding in both basic and translational breast cancer research. The interactive, multidisciplinary research environment has provided the investigator opportunities to interact with pathologists and oncologists, thus fostering future success as an independent breast cancer researcher. To date, all tasks, as outlined in the Statement of Work, are on schedule.
- Anatomy and Physiology
- Medicine and Medical Research