Mouse cDNA microarray analysis uncovers Slug targets in mouse embryonic fibroblasts.
There is a need to reveal mechanisms that account for maintenance of the mesenchymal phenotype in normal development and cancer. Slug (approved gene symbol Snai2), a member of the Snail gene family of zinc-finger transcription factors, is believed to function in the maintenance of the nonepithelial phenotype. This study identified candidate Slug target genes linked to Slug gene suppression in primary mouse embryonic fibroblasts. Expression analyses were performed with a mouse cDNA microarray (Mousechip-CNIO) containing 15,000 clones. A total of 15 novel Slug target species were validated by real-time PCR or Western analyses. These included self-renewal genes (Bmi1, Nanog, Gfi1), epithelial-mesenchymal genes (Tcfe2a, Ctnb1, Sin3a, Hdac1, Hdac2, Muc1, Cldn11), survival genes (Bcl2, Bbc3), and cell cycle/damage genes (Cdkn1a, Rbl1, Mdm2). Expression patterns were studied in wild-type MEFs and Slug-deficient MEFs. Slug-complementation studies recovered aberrant gene expression in cells lacking Slug, indicating that these genes were regulated directly by Slug. These results highlight their potential roles in mediating Slug function in mesenchymal cells and may help to identify novel therapeutic biomarkers in cancers linked to Slug.
Bermejo-Rodríguez
Camino
C
Laboratorio 13, Instituto de Biología Molecular y Celular del Cáncer, CSIC/Universidad de Salamanca, Campus Unamuno, 37007 Salamanca, Spain.
Pérez-Caro
María
M
Pérez-Mancera
Pedro Antonio
PA
Sánchez-Beato
Margarita
M
Piris
Miguel A
MA
Sánchez-García
Isidro
I
D000818:Animals; D014408:Biomarkers, Tumor / Q000235:genetics; D002454:Cell Differentiation / Q000235:genetics; D004249:DNA Damage / Q000235:genetics; D004622:Embryo, Mammalian / Q000166:cytology / Q000502:physiology*; D005347:Fibroblasts / Q000166:cytology / Q000502:physiology*; D020869:Gene Expression Profiling / Q000379:methods; D005786:Gene Expression Regulation / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D018816:Genes, cdc / Q000502:physiology; D005816:Genetic Complementation Test / Q000379:methods; D051379:Mice; D009369:Neoplasms / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism
D014408:Biomarkers, Tumor; C000604449:Snai2 protein, mouse; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors