Stem Cell Research (Sep 2015)

Prolactin/Jak2 directs apical/basal polarization and luminal linage maturation of mammary epithelial cells through regulation of the Erk1/2 pathway

  • Fengming Liu,
  • Andrew Pawliwec,
  • Zhenqian Feng,
  • Zivart Yasruel,
  • Jean-Jacques Lebrun,
  • Suhad Ali

DOI
https://doi.org/10.1016/j.scr.2015.08.001
Journal volume & issue
Vol. 15, no. 2
pp. 376 – 383

Abstract

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Tissue development/remodeling requires modulations in both cellular architecture and phenotype. Aberration in these processes leads to tumorigenesis. During the pregnancy/lactation cycle the mammary epithelial cells undergo complex morphological and phenotypic programs resulting in the acquisition of apical/basal (A/B) polarization and cellular maturation necessary for proper lactation. Still the hormonal regulations and cellular mechanisms controlling these events are not entirely elucidated. Here we show that prolactin (PRL)/Jak2 pathway in mammary epithelial cells uniquely signals to establish A/B polarity as determined by the apical localization of the tight junction protein zona occludens 1 (ZO-1) and the basal/lateral localization of E-cadherin, and the apical trafficking of lipid droplets. As well, our results indicate that this pathway regulates mammary stem cell hierarchy by inducing the differentiation of luminal progenitor (EpCAMhi/CD49fhi) cells to mature luminal (EpCAMhi/CD49flow) cells. Moreover, our data indicate that PRL/Jak2 coordinates both of these cellular events through limiting the mitogen activated protein kinase (Erk1/2) pathway. Together our findings define a novel unifying mechanism coupling mammary epithelial cell A/B polarization and terminal differentiation.

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