title: c-MYC-induced sebaceous gland differentiation is controlled by an androgen receptor/p53 axis.
abstract: Although the sebaceous gland (SG) plays an important role in skin function, the mechanisms regulating SG differentiation and carcinoma formation are poorly understood. We previously reported that c-MYC overexpression stimulates SG differentiation. We now demonstrate roles for the androgen receptor (AR) and p53. MYC-induced SG differentiation was reduced in mice lacking a functional AR. High levels of MYC triggered a p53-dependent DNA damage response, leading to accumulation of proliferative SG progenitors and inhibition of AR signaling. Conversely, testosterone treatment or p53 deletion activated AR signaling and restored MYC-induced differentiation. Poorly differentiated human sebaceous carcinomas exhibited high p53 and low AR expression. Thus, the consequences of overactivating MYC in the SG depend on whether AR or p53 is activated, as they form a regulatory axis controlling proliferation and differentiation.
authors: Wellcome Trust-Medical Research Council Stem Cell Institute SCI, University of Cambridge, Tennis Court Road, Cambridge CB2 1QR, UK.
authors: Denny L
authors: DL
authors: Cottle
authors: Kai
authors: K
authors: Kretzschmar
authors: Pawel J
authors: PJ
authors: Schweiger
authors: Sven R
authors: SR
authors: Quist
authors: Harald P
authors: HP
authors: Gollnick
authors: Ken
authors: K
authors: Natsuga
authors: Satoru
authors: S
authors: Aoyagi
authors: Fiona M
authors: FM
authors: Watt
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D011944:Receptors, Androgen / Q000235:genetics / Q000378:metabolism*; D012626:Sebaceous Gland Neoplasms / Q000378:metabolism / Q000473:pathology; D012627:Sebaceous Glands / Q000166:cytology / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D013629:Tamoxifen / Q000031:analogs & derivatives / Q000494:pharmacology; D013739:Testosterone / Q000494:pharmacology; D016159:Tumor Suppressor Protein p53 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger; D011944:Receptors, Androgen; D016159:Tumor Suppressor Protein p53; D013629:Tamoxifen; C016601:afimoxifene; D013739:Testosterone
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