The luminal progenitor compartment of the normal human mammary gland constitutes a unique site of telomere dysfunction.

Nagarajan Kannan, Nazmul Huda, Liren Tu, Radina Droumeva, Geraldine Aubert, Elizabeth Chavez, Ryan R Brinkman, Peter Lansdorp, Joanne Emerman, Satoshi Abe, Connie Eaves, David Gilley

Index: Stem Cell Reports 1 , 28-37, (2013)

Full Text: HTML

Abstract

Telomeres are essential for genomic integrity, but little is known about their regulation in the normal human mammary gland. We now demonstrate that a phenotypically defined cell population enriched in luminal progenitors (LPs) is characterized by unusually short telomeres independently of donor age. Furthermore, we find that multiple DNA damage response proteins colocalize with telomeres in >95% of LPs but in <5% of basal cells. Paradoxically, 25% of LPs are still capable of exhibiting robust clonogenic activity in vitro. This may be partially explained by the elevated telomerase activity that was also seen only in LPs. Interestingly, this potential telomere salvage mechanism declines with age. Our findings thus reveal marked differences in the telomere biology of different subsets of primitive normal human mammary cells. The chronically dysfunctional telomeres unique to LPs have potentially important implications for normal mammary tissue homeostasis as well as the development of certain breast cancers.