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Publication : Dose and context dependent effects of Myc on epidermal stem cell proliferation and differentiation.

First Author  Berta MA Year  2010
Journal  EMBO Mol Med Volume  2
Issue  1 Pages  16-25
PubMed ID  20043278 Mgi Jnum  J:232315
Mgi Id  MGI:5776472 Doi  10.1002/emmm.200900047
Citation  Berta MA, et al. (2010) Dose and context dependent effects of Myc on epidermal stem cell proliferation and differentiation. EMBO Mol Med 2(1):16-25
abstractText  Myc is activated in many tumours, yet, paradoxically, stimulates differentiation in mammalian epidermis. To test whether the epidermis responds differently to different levels of Myc, we treated K14MycER transgenic mice with a range of concentrations of the inducing agent, 4-hydroxy-tamoxifen (4OHT). Proliferation was stimulated at all levels of Myc activity; sebocyte differentiation was stimulated at low and intermediate levels; and interfollicular epidermal differentiation at intermediate and high levels. Mutational inactivation of the Myc p21 activated kinase 2 (PAK2) phosphorylation sites increased Myc activity and further enhanced epidermal differentiation. We conclude that Myc induced differentiation acts as a fail-safe device to prevent uncontrolled proliferation and neoplastic conversion of epidermal stem cells expressing high levels of Myc.
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