title: Transcriptional regulation by normal epithelium of premalignant to malignant progression in Barrett's esophagus.
abstract: In carcinogenesis, intercellular interactions within and between cell types are critical but remain poorly understood. We present a study on intercellular interactions between normal and premalignant epithelial cells and their functional relevance in the context of premalignant to malignant progression in Barrett's esophagus. Using whole transcriptome profiling we found that in the presence of normal epithelial cells, dysplastic cells but not normal cells, exhibit marked down-regulation of a number of key signaling pathways, including the transforming growth factor beta (TGFβ) and epithelial growth factor (EGF). Functional assays revealed both cell types showed repressed proliferation and significant changes in motility (speed, displacement and directionality) as a result of interactions between the two cell types. Cellular interactions appear to be mediated through both direct cell-cell contact and secreted ligands. The findings of this study are important in that they reveal, for the first time, the effects of cellular communication on gene expression and cellular function between premalignant (dysplastic) epithelial cells and their normal counterparts.
authors.affiliation: Center for Biosignatures Discovery Automation, The Biodesign Institute, Arizona State University, P.O. Box 876501, Tempe, AZ 85287-6501, United States.
authors.forename: Jia
authors.initials: J
authors.lastname: Zeng
authors.affiliation: Center for Biosignatures Discovery Automation, The Biodesign Institute, Arizona State University, P.O. Box 876501, Tempe, AZ 85287-6501, United States.
authors.forename: Laimonas
authors.initials: L
authors.lastname: Kelbauskas
authors.affiliation: Center for Biosignatures Discovery Automation, The Biodesign Institute, Arizona State University, P.O. Box 876501, Tempe, AZ 85287-6501, United States.
authors.forename: Aida
authors.initials: A
authors.lastname: Rezaie
authors.affiliation: Center for Biosignatures Discovery Automation, The Biodesign Institute, Arizona State University, P.O. Box 876501, Tempe, AZ 85287-6501, United States.
authors.forename: Kristen
authors.initials: K
authors.lastname: Lee
authors.affiliation: Center for Biosignatures Discovery Automation, The Biodesign Institute, Arizona State University, P.O. Box 876501, Tempe, AZ 85287-6501, United States.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Ueberroth
authors.affiliation: Center for Biosignatures Discovery Automation, The Biodesign Institute, Arizona State University, P.O. Box 876501, Tempe, AZ 85287-6501, United States.
authors.forename: Weimin
authors.initials: W
authors.lastname: Gao
authors.affiliation: Center for Biosignatures Discovery Automation, The Biodesign Institute, Arizona State University, P.O. Box 876501, Tempe, AZ 85287-6501, United States.
authors.forename: Dmitry
authors.initials: D
authors.lastname: Derkach
authors.affiliation: Center for Biosignatures Discovery Automation, The Biodesign Institute, Arizona State University, P.O. Box 876501, Tempe, AZ 85287-6501, United States.
authors.forename: Thai
authors.initials: T
authors.lastname: Tran
authors.affiliation: Center for Biosignatures Discovery Automation, The Biodesign Institute, Arizona State University, P.O. Box 876501, Tempe, AZ 85287-6501, United States.
authors.forename: Dean
authors.initials: D
authors.lastname: Smith
authors.affiliation: Center for Biosignatures Discovery Automation, The Biodesign Institute, Arizona State University, P.O. Box 876501, Tempe, AZ 85287-6501, United States.
authors.forename: Kimberly J
authors.initials: KJ
authors.lastname: Bussey
authors.affiliation: Center for Biosignatures Discovery Automation, The Biodesign Institute, Arizona State University, P.O. Box 876501, Tempe, AZ 85287-6501, United States.
authors.forename: Deirdre R
authors.initials: DR
authors.lastname: Meldrum
mesh_terms: D001471:Barrett Esophagus / Q000473:pathology*; D002450:Cell Communication; D002460:Cell Line; D045744:Cell Line, Tumor; D018920:Coculture Techniques; D017077:Culture Media, Conditioned; D018450:Disease Progression; D004815:Epidermal Growth Factor / Q000378:metabolism; D004848:Epithelium / Q000473:pathology; D005786:Gene Expression Regulation; D006801:Humans; D017423:Sequence Analysis, RNA; D014158:Transcription, Genetic; D059467:Transcriptome; D016212:Transforming Growth Factor beta / Q000378:metabolism
chemical_list: D017077:Culture Media, Conditioned; D016212:Transforming Growth Factor beta; D004815:Epidermal Growth Factor