Determinants of Human Breast Epithelial Cell Estrogen Expression and Differentiation: Organization and Environment

摘要

Breast cancer presumabl& originates in an estrogen receptor-positive (ER+), estrogen (E2)-responsive epithelial cell within organized human breast tissue. Paradoxically there is an exceedingly low level of, and few cells expressing, ER in normal breast tissue, and human breast epithelial (HBE) cell lines lack ER and do not respond to E2. Our hypothesis is that human breast parenchymal epithelial cell-cell interactions and epithelial stromal interactions are critical in vitro determinants of ER expression and biochemical differentiation. Our prior progress reported failure to demonstrate ER expression using established HBE cell lines organized into three- dimensional structures, conglomerates, resembling in vivo organization, and success developing and characterizing breast stromal cell resources, part of a submitted manuscript. We now report progress establishing and characterizing epithelial cells from reduction mammoplasty, benign and tumor breast tissues. Some, including cells from a tissue with demonstrable epithelial cell ER expression, failed to express ER under traditional culture conditions and in conglomerates and to exhibit responsiveness to estrogen growth. Importantly, epithelial cells from one reduction mammoplasty specimen do express ER under traditional culture conditions and in conglomerates. The latter provides evidence of significant progress towards our goal of endogenous ER expression in reduction mammoplasty- derived human breast epithelial cells.