Cellular Consequences of Telomere Shortening in Histologically Normal Breast Tissues
Abstract
Three independent sets of normal breast tissues without evidence of cancer, either obtained from patients undergoing reduction mammoplasty or in women at time of autopsy, have been analyzed. The postdoctoral trainee has shown that moderate to dramatic telomere shortening occurs specifically in luminal epithelial cells, but not in myoepithelial cells, in the majority of histologically normal terminal ductal lobular units. However, the extent and degree of telomere 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, ongoing experiments are assessing 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 for the trainee. The interactive, multidisciplinary research environment at Johns Hopkins has provided the investigator opportunities to interact with pathologists, oncologists and epidemiologists, thus fostering future success as an independent translational breast cancer researcher.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 2012
- Accession Number
- ADA567170
Entities
People
- Alan K Meeker
- Christopher M Heaphy
- Pedram Argani
Organizations
- Johns Hopkins University