title: Prolactin/Jak2 directs apical/basal polarization and luminal linage maturation of mammary epithelial cells through regulation of the Erk1/2 pathway.
abstract: 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.
authors: Division of Hematology, Department of Medicine, Cancer Research Program, McGill University Health Centre, Montreal, QC, H4A 3J1, Canada.
authors: Fengming
authors: F
authors: Liu
authors: Division of Hematology, Department of Medicine, Cancer Research Program, McGill University Health Centre, Montreal, QC, H4A 3J1, Canada.
authors: Andrew
authors: A
authors: Pawliwec
authors: Division of Hematology, Department of Medicine, Cancer Research Program, McGill University Health Centre, Montreal, QC, H4A 3J1, Canada.
authors: Zhenqian
authors: Z
authors: Feng
authors: Division of Hematology, Department of Medicine, Cancer Research Program, McGill University Health Centre, Montreal, QC, H4A 3J1, Canada.
authors: Zivart
authors: Z
authors: Yasruel
authors: Division of Medical Oncology, Department of Medicine, Cancer Research Program, McGill University Health Centre, Montreal, QC, H4A 3J1, Canada.
authors: Jean-Jacques
authors: JJ
authors: Lebrun
authors: Division of Hematology, Department of Medicine, Cancer Research Program, McGill University Health Centre, Montreal, QC, H4A 3J1, Canada. Electronic address: suhad.ali@mcgill.ca.
authors: Suhad
authors: S
authors: Ali
mesh_terms: D000818:Animals; D000951:Antigens, Neoplasm / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000378:metabolism; D018929:Cell Culture Techniques; D019070:Cell Lineage; D016764:Cell Polarity; D002478:Cells, Cultured; D000071858:Epithelial Cell Adhesion Molecule; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism*; D005260:Female; D039503:Integrin alpha6 / Q000378:metabolism; D053614:Janus Kinase 2 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D020935:MAP Kinase Signaling System; D008321:Mammary Glands, Animal / Q000166:cytology; D051379:Mice; D011388:Prolactin / Q000378:metabolism*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism
chemical_list: D000951:Antigens, Neoplasm; D015815:Cell Adhesion Molecules; D000071858:Epithelial Cell Adhesion Molecule; D039503:Integrin alpha6; D034741:RNA, Small Interfering; D011388:Prolactin; C507926:Jak2 protein, mouse; D053614:Janus Kinase 2
keywords: Differentiation; Jak/Stat pathway; Mammary stem/progenitor cells; Morphogenesis