title: Transcriptional networks in epithelial-mesenchymal transition.
abstract: BACKGROUND
  Epithelial-mesenchymal transition (EMT) changes polarized epithelial cells into migratory phenotypes associated with loss of cell-cell adhesion molecules and cytoskeletal rearrangements. This form of plasticity is seen in mesodermal development, fibroblast formation, and cancer metastasis.
  
  
  RESULTS
  Here we identify prominent transcriptional networks active during three time points of this transitional process, as epithelial cells become fibroblasts. DNA microarray in cultured epithelia undergoing EMT, validated in vivo, were used to detect various patterns of gene expression. In particular, the promoter sequences of differentially expressed genes and their transcription factors were analyzed to identify potential binding sites and partners. The four most frequent cis-regulatory elements (CREs) in up-regulated genes were SRY, FTS-1, Evi-1, and GC-Box, and RNA inhibition of the four transcription factors, Atf2, Klf10, Sox11, and SP1, most frequently binding these CREs, establish their importance in the initiation and propagation of EMT. Oligonucleotides that block the most frequent CREs restrain EMT at early and intermediate stages through apoptosis of the cells.
  
  
  CONCLUSIONS
  Our results identify new transcriptional interactions with high frequency CREs that modulate the stability of cellular plasticity, and may serve as targets for modulating these transitional states in fibroblasts.
authors: Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee, United States of America.
authors: Christo
authors: C
authors: Venkov
authors: David
authors: D
authors: Plieth
authors: Terri
authors: T
authors: Ni
authors: Amitava
authors: A
authors: Karmaker
authors: Aihua
authors: A
authors: Bian
authors: Alfred L
authors: AL
authors: George
authors: Eric G
authors: EG
authors: Neilson
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D015415:Biomarkers / Q000378:metabolism; D002460:Cell Line; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects / Q000235:genetics*; D005355:Fibrosis; D055785:Gene Knockdown Techniques; D053263:Gene Regulatory Networks / Q000187:drug effects / Q000235:genetics*; D007687:Kidney Tubules, Proximal / Q000166:cytology / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D020411:Oligonucleotide Array Sequence Analysis; D015203:Reproducibility of Results; D020218:Response Elements / Q000187:drug effects / Q000235:genetics; D014157:Transcription Factors / Q000172:deficiency / Q000235:genetics; D014158:Transcription, Genetic / Q000187:drug effects / Q000235:genetics; D016212:Transforming Growth Factor beta / Q000494:pharmacology
chemical_list: D015415:Biomarkers; D014157:Transcription Factors; D016212:Transforming Growth Factor beta