EIF4E threshold levels differ in governing normal and neoplastic expansion of mammary stem and luminal progenitor cells.

ABSTRACT: Translation initiation factor eIF4E mediates normal cell proliferation, yet induces tumorigenesis when overexpressed. The mechanisms by which eIF4E directs such distinct biologic outputs remain unknown. We found that mouse mammary morphogenesis during pregnancy and lactation is accompanied by increased cap-binding capability of eIF4E and activation of the eIF4E-dependent translational apparatus, but only subtle oscillations in eIF4E abundance. Using a transgenic mouse model engineered so that lactogenic hormones stimulate a sustained increase in eIF4E abundance in stem/progenitor cells of lactogenic mammary epithelium during successive pregnancy/lactation cycles, eIF4E overexpression increased self-renewal, triggered DNA replication stress, and induced formation of premalignant and maligna

SUBMITTER: Avdulov S 

PROVIDER: S-EPMC4333007 | biostudies-literature | 2015 Feb

REPOSITORIES: biostudies-literature