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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Nelson, Celeste M. Muschler, John L. Vonderhaar, Barbara K. Xu, Ren Veiseh, Mandana Bissell, Mina J. |
| Description | Author Affiliation: Xu R ( Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA) |
| Abstract | Epithelial cells, once dissociated and placed in two-dimensional (2D) cultures, rapidly lose tissue-specific functions. We showed previously that in addition to prolactin, signaling by laminin-111 was necessary to restore functional differentiation of mammary epithelia. Here, we elucidate two additional aspects of laminin-111 action. We show that in 2D cultures, the prolactin receptor is basolaterally localized and physically segregated from its apically placed ligand. Detachment of the cells exposes the receptor to ligation by prolactin leading to signal transducers and activators of transcription protein 5 (STAT5) activation, but only transiently and not sufficiently for induction of milk protein expression. We show that laminin-111 reorganizes mammary cells into polarized acini, allowing both the exposure of the prolactin receptor and sustained activation of STAT5. The use of constitutively active STAT5 constructs showed that the latter is necessary and sufficient for chromatin reorganization and β-casein transcription. These results underscore the crucial role of continuous laminin signaling and polarized tissue architecture in maintenance of transcription factor activation, chromatin organization, and tissue-specific gene expression. |
| ISSN | 00219525 |
| e-ISSN | 15408140 |
| Journal | The Journal of Cell Biology |
| Issue Number | 1 |
| Volume Number | 184 |
| Language | English |
| Publisher | Rockefeller University Press (United States) |
| Publisher Date | 2009-01-12 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Chromatin Assembly And Disassembly Mammary Glands, Animal Physiology STAT5 Transcription Factor Acetylation Animals Caseins Metabolism Cell Culture Techniques Cell Differentiation Dystroglycans Histones Janus Kinase 2 Laminin Pharmacology Cytology Mice Milk Proteins Phosphorylation Prolactin Promoter Regions, Genetic RNA, Messenger Receptors, Prolactin Genetics Signal Transduction Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. Cell Biology |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cell Biology Medicine |
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