Expression data of pre-stasis cultured HMEC

We have generated a large collection of normal human mammary epithelial cell strains from women aged 16 to 91 years, derived from primary tissues, to enable functional and molecular interrogation of aging. We demonstrate in finite-lifespan cultured and uncultured epithelial cells that aging is associated with reduction of myoepithelial cells and with increases in luminal cells expressing keratin 14 and integrin 6, traits that are expressed exclusively in myoepithelial cells in women under 30. We find that changes to the luminal lineage result from age-dependent expansion of multipotent progenitors that bear defects resulting in incompletely differentiated luminal cells. These findings were verified in vivo in normal breast tissues. Myoepithelial cells have been suggested to act as tumor suppressors, and progenitor cells are implicated as the etiological roots of mammary carcinomas. Thus with aging there is a shift in the balance of luminal/myoepithelial lineages, and changes in the functional spectrum of multipotent progenitors, which presages increased potential for malignant transformation.

52

Garbe JC, Pepin F, Pelissier FA, Sputova K, Fridriksdottir AJ, Guo DE, Villadsen R, Park M, Petersen OW, Borowsky AD, Stampfer MR, Labarge MA