Stromal-Epithelial Interactions and Tamoxifen-Sensitivity: A Bench-to- Bedside Model of Chemoprevention

摘要

The microenvironment of the breast likely plays a critical role in changes to cytology during the development of cancer. Understanding of changes to the genetic as well as broader biochemical constituents of individual cells or cell types may have greater influence in our ability to detect and or track cancer development. It is likely that these changes are dynamic and affected by external stimuli including therapeutic regimes. This work examined changes in the methylation profile of estrogen responsive genes (estrogen receptor and progesterone receptor) as well as establishing early protocols for examination of tissue-level steroids that may function through these important receptors. Finally, we initiated studies to evaluate the role of changing environment on tissue development by isolating, culturing and differentiating adipose derived pluripotent (stem) cells from the breast tissue. The results of these studies showed that estrogen receptor methylation status does not change with respect to tamoxifen treatment. Current focus on progesterone metyhylation will soon determine if this is treatment has effect on this gene or not. Finally, we have demonstrated through our pilot study that changes in breast tissue level steroids are likely related to body mass index and menopausal status.