STANDARD_NAME DAZARD_UV_RESPONSE_CLUSTER_G4 SYSTEMATIC_NAME M10885 COLLECTION C2:CGP MSIGDB_URL https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/DAZARD_UV_RESPONSE_CLUSTER_G4 NAMESPACE HUMAN_SEQ_ACCESSION DESCRIPTION_BRIEF Cluster G4: genes increasingly up-regulated in NHEK cells (normal keratinocyte) after 12 h time point after UV-B irradiation. DESCRIPTION_FULL To gain insight into the transformation of epidermal cells into squamous carcinoma cells (SCC), we compared the response to ultraviolet B radiation (UVB) of normal human epidermal keratinocytes (NHEK) versus their transformed counterpart, SCC, using biological and molecular profiling. DNA microarray analyses (Affymetrix), approximately 12000 genes) indicated that the major group of upregulated genes in keratinocytes fall into three categories: (i). antiapoptotic and cell survival factors, including chemokines of the CXC/CC subfamilies (e.g. IL-8, GRO-1, -2, -3, SCYA20), growth factors (e.g. HB-EGF, CTGF, INSL-4), and proinflammatory mediators (e.g. COX-2, S100A9), (ii). DNA repair-related genes (e.g. GADD45, ERCC, BTG-1, Histones), and (iii). ECM proteases (MMP-1, -10). The major downregulated genes are DeltaNp63 and PUMILIO, two potential markers for the maintenance of keratinocyte stem cells. NHEK were found to be more resistant than SCC to UVB-induced apoptosis and this resistance was mainly because of the protection from cell death by secreted survival factors, since it can be transferred from NHEK to SCC cultures by the conditioned medium. Whereas the response of keratinocytes to UVB involved regulation of key checkpoint genes (p53, MDM2, p21(Cip1), DeltaNp63), as well as antiapoptotic and DNA repair-related genes - no or little regulation of these genes was observed in SCC. The effect of UVB on NHEK and SCC resulted in upregulation of 251 and 127 genes, respectively, and downregulation of 322 genes in NHEK and 117 genes in SCC. To further analyse these changes, we used a novel unsupervised coupled two-way clustering method that allowed the identification of groups of genes that clearly partitioned keratinocytes from SCC, including a group of genes whose constitutive expression levels were similar before UVB. This allowed the identification of discriminating genes not otherwise revealed by simple static comparison in the absence of UVB irradiation. The implication of the changes in gene profile in keratinocytes for epithelial cancer is discussed. PMID 12771951 GEOID AUTHORS Dazard JE,Gal H,Amariglio N,Rechavi G,Domany E,Givol D CONTRIBUTOR John Newman CONTRIBUTOR_ORG University of Washington EXACT_SOURCE Table 2S: Cluster#=4 FILTERED_BY_SIMILARITY EXTERNAL_NAMES_FOR_SIMILAR_TERMS EXTERNAL_DETAILS_URL SOURCE_MEMBERS AB006867,AF078077,D64137,D64142,HG2259-HT2348,J02902,J03191,L19779,M92843,U47634,U92315,X00734,X02344,X04106,X07820,X68277,X69550,X71345,Y00486,Y16790,Z93930 GENE_SYMBOLS SOX15,GADD45B,CDKN1C,H1-10,,PPP2R1A,PFN1,H2AC18,ZFP36,TUBB3,SULT2B1,TUBB4A,TUBB4B,CAPNS1,MMP10,DUSP1,ARHGDIA,PRSS3,APRT,KRT34,XBP1 FOUNDER_NAMES