title: Transgenic overexpression of cdx1b induces metaplastic changes of gene expression in zebrafish esophageal squamous epithelium.
abstract: Cdx2 has been suggested to play an important role in Barrett's esophagus or intestinal metaplasia (IM) in the esophagus. To investigate whether transgenic overexpression of cdx1b, the functional equivalent of mammalian Cdx2 in zebrafish, may lead to IM of zebrafish esophageal squamous epithelium, a transgenic zebrafish system was developed by expressing cdx1b gene under the control of zebrafish keratin 5 promoter (krt5p). Gene expression in the esophageal squamous epithelium of wild-type and transgenic zebrafish was analyzed by Affymetrix microarray and confirmed by in situ hybridization. Morphology, mucin expression, cell proliferation, and apoptosis were analyzed by hematoxylin & eosin (HE) staining, Periodic acid Schiff (PAS) Alcian blue staining, proliferating cell nuclear antigen (PCNA) immunohistochemical staining, and TUNEL assay as well. cdx1b was found to be overexpressed in the nuclei of esophageal squamous epithelial cells of the transgenic zebrafish. Ectopic expression of cdx1b disturbed the development of this epithelium in larval zebrafish and induced metaplastic changes in gene expression in the esophageal squamous epithelial cells of adult zebrafish, that is, up-regulation of intestinal differentiation markers and down-regulation of squamous differentiation markers. However, cdx1b failed to induce histological IM, or to modulate cell proliferation and apoptosis in the squamous epithelium of adult transgenic zebrafish.
authors.affiliation: Cancer Research Program, Department of Biology, Julius L. Chambers Biomedical/Biotechnology Research Institute, North Carolina Central University , Durham, NC 27707, USA.
authors.forename: Bo
authors.initials: B
authors.lastname: Hu
authors.forename: Hao
authors.initials: H
authors.lastname: Chen
authors.forename: Xiuping
authors.initials: X
authors.lastname: Liu
authors.forename: Chengjin
authors.initials: C
authors.lastname: Zhang
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Cole
authors.forename: Ju-Ahng
authors.initials: JA
authors.lastname: Lee
authors.forename: Xiaoxin
authors.initials: X
authors.lastname: Chen
mesh_terms: D000818:Animals; D001471:Barrett Esophagus / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D049109:Cell Proliferation; D004848:Epithelium / Q000378:metabolism / Q000473:pathology; D004947:Esophagus / Q000378:metabolism / Q000473:pathology*; D018507:Gene Expression Regulation, Developmental; D015972:Gene Expression Regulation, Neoplastic; D018398:Homeodomain Proteins / Q000235:genetics* / Q000378:metabolism; D017403:In Situ Hybridization; D053555:Keratin-5 / Q000235:genetics / Q000378:metabolism; D007814:Larva; D008679:Metaplasia / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D023421:Models, Animal; D009077:Mucins / Q000235:genetics / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic; D015027:Zebrafish; D029961:Zebrafish Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: C529211:Cdx1b protein, zebrafish; D018398:Homeodomain Proteins; D053555:Keratin-5; D009077:Mucins; D029961:Zebrafish Proteins