title: Paracrine effect of TGF-beta1 on downregulation of gap junctional intercellular communication between human dermal fibroblasts.
abstract: Disruption of gap junctional intercellular communication (GJIC) is associated with tumor progression during multistage carcinogenesis. A coordinated interaction of epithelial tumor cells with the stromal environment via growth factors is a prerequisite for tumor invasion. Here, the involvement of growth factors in downregulation of homologous GJIC of dermal fibroblasts, used as model for stromal cells, was examined. Tumor cell derived transforming growth factor-beta1 (TGF-beta1), having oncogenic activities at late stages of carcinogenesis, was identified as being responsible for downregulation of GJIC via an increase in the level of reactive oxygen species in stromal fibroblasts. Lowering the level of reactive oxygen species by antioxidants, such as the cell-permeable N-acetyl-L-cysteine, prevented TGF-beta1-mediated downregulation of intercellular communication between confluent fibroblasts.
authors.affiliation: Institute for Biochemistry and Molecular Biology I, Heinrich-Heine-University, D-40225 Düsseldorf, Germany.
authors.forename: Dominik
authors.initials: D
authors.lastname: Stuhlmann
authors.forename: Holger
authors.initials: H
authors.lastname: Steinbrenner
authors.forename: Bernhard
authors.initials: B
authors.lastname: Wendlandt
authors.forename: Dragana
authors.initials: D
authors.lastname: Mitic
authors.forename: Helmut
authors.initials: H
authors.lastname: Sies
authors.forename: Peter
authors.initials: P
authors.lastname: Brenneisen
mesh_terms: D002450:Cell Communication / Q000502:physiology*; D002478:Cells, Cultured; D015536:Down-Regulation / Q000502:physiology*; D004797:Enzyme-Linked Immunosorbent Assay; D005347:Fibroblasts / Q000166:cytology; D017629:Gap Junctions / Q000502:physiology*; D006801:Humans; D012867:Skin / Q000166:cytology*; D016212:Transforming Growth Factor beta / Q000502:physiology*
chemical_list: D016212:Transforming Growth Factor beta