Abstract A24: Age- and lineage-dependent gene expression is maintained by microenvironment imposed epigenetic states in human mammary epithelial cells

Normal healthy tissues show changing patterns of gene expression as a consequence of aging, and there is a functional cost to these changes that can be relevant to disease pathology. The most obvious age-related disease in breast is cancer, with the large majority of newly diagnosed breast cancer occuring in women over 50. We have shown that breast gene expression changes that occur with age have functional consequences in the epithelial progenitor and differentiated cells, i.e, a decline of the myoepithelial lineage, loss of luminal cell specificity, and accumulation of differentiation defective multipotent progenitor cells. We have hypothesized that these tissue-level changes make older epithelia more susceptible to transformation. Because gene expression patterns reflect the wiring and response diagrams of cells, it is of central importance to understand the origins of age-related transcriptomes. In our studies, early passage normal human mammary epithelial cells (HMEC) show age-dependent functional and molecular hallmarks consistent with in vivo, suggesting that the underlying gene expression patterns are metastable. DNA methylation is a stable, but malleable, form of epigenetic regulation that may underpin these biologically metastable states. Genome-wide analysis of primary epithelia was used to identify a set of genes that exhibit age- and lineage-specific expression that was inversely correlated with promoter CpG methylation. Chemical perturbation of DNA methylation i...
Source: Molecular Cancer Research - Category: Cancer & Oncology Authors: Tags: Differentiation Hierarchy and Cancer: Poster Presentations - Proffered Abstracts Source Type: research