Human Gene Set: CHEBOTAEV_GR_TARGETS_DN

For the Mouse gene set with the same name, see CHEBOTAEV_GR_TARGETS_DN

Standard name CHEBOTAEV_GR_TARGETS_DN
Systematic name M7876
Brief description Genes down-regulated in follicular epithelial stem cells after transgenic expression of GR [GeneID=2908] under control of the keratin5 (K5) [GeneID=3852] promoter.
Full description or abstract Glucocorticoids are potent inhibitors of mouse skin tumorigenesis. The glucocorticoid control of cellular functions is mediated via the glucocorticoid receptor (GR), a well-known transcription factor. Recently, we generated transgenic mice overexpressing GR under control of the keratin5 (K5) promoter, and showed that K5.GR animals are resistant to skin carcinogenesis. Follicular epithelial stem cells (SCs), located in the bulge region of the hair follicle, are believed to be one of the target cells for skin carcinogenesis. We found that the number of putative hair follicle SC detected as label-retaining cells was significantly less in the K5.GR transgenics compared to wild type (w.t.) littermates. We also showed that GR overexpression led to a reduction in the clonogenicity of the follicular epithelial SCs. We evaluated the global effect of GR on gene expression in a population of follicular SC-enriched bulge keratinocytes isolated by fluorescence activated cell sorting. We found that GR affected the expression of numerous bulge SC 'signature' genes, genes involved in the maintenance of SC and progenitor cells of non-epidermal origin and proapoptotic genes. Our findings underscore the important role of GR signaling in the homeostasis of follicular epithelial SCs, and suggest that the reduction in their number may underlie the tumor suppressor effect of GR in the skin.
Collection C2: Curated
      CGP: Chemical and Genetic Perturbations
Source publication Pubmed 17146443   Authors: Chebotaev D,Yemelyanov A,Zhu L,Lavker RM,Budunova I
Exact source Table 2S
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Source species Mus musculus
Contributed by Leona Saunders (MSigDB Team)
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AFFY_Mouse430
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