title: Correlation between the high expression of C/EBPbeta protein in F442A cells and their relative resistance to antiadipogenic action of TCDD in comparison to 3T3-L1 cells.
abstract: We compared the ability of two clonally derived murine preadipocyte cell lines, 3T3-L1(L1) and 3T3-F442A (F442A), to differentiate after treatment by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), and found that the former cell line was clearly suppressed by TCDD but the latter was not. It was initially postulated that the easiest way to explain the lack of response to TCDD in F442A cells could be an alteration in aryl hydrocarbon receptor (AhR) functionality. This hypothesis was tested first, but no differences were found in the levels or functions of AhR. To find an alternate explanation for such a differential effect of TCDD, we tested the action of several diagnostic agents on the process of adipocyte differentiation of these two cells. No differences were found between these two lines of cells in the susceptibility to the antiadipogenic action of 12-0-tetradecanoylphorbol-13-acetate (TPA), or to TNFalpha, indicating that the basic biochemical components engaged in the antiadipogenic actions of these agents in these two cell lines are similar. In contrast, F442A cells were found to be more resistant to the antiadipogenic action of EGF or TGFbeta than L1 cells which were tested side by side. Based on the knowledge that TNFalpha preferentially affects C/EBPalpha and that TGFbeta specifically controls C/EBPbeta and delta in their antiadipogenic action, we hypothesized that the major cause for the differential response of these two similar cell lines could be the insensitivity of C/EBPbeta and/or delta of F442A cells to the action of TCDD. We could obtain supporting data for this hypothesis, showing that in F442A cells, the level of C/EBPbeta is already high even before the addition of adipocyte differentiation factors and that TCDD did not cause any significant changes in the titer of C/EBPbeta.
authors.affiliation: Department of Environmental Toxicology, University of California, Davis, CA 95616, USA.
authors.forename: Phillip C C
authors.initials: PC
authors.lastname: Liu
authors.forename: Maria J
authors.initials: MJ
authors.lastname: Moreno-Aliaga
authors.forename: Debra Y
authors.initials: DY
authors.lastname: Dunlap
authors.forename: Xiao-ming
authors.initials: XM
authors.lastname: Hu
authors.forename: Michael S
authors.initials: MS
authors.lastname: Denison
authors.forename: Fumio
authors.initials: F
authors.lastname: Matsumura
mesh_terms: D016475:3T3 Cells; D017667:Adipocytes / Q000166:cytology / Q000187:drug effects*; D000818:Animals; D015152:Blotting, Northern; D015139:Blotting, Southern; D022782:CCAAT-Enhancer-Binding Protein-beta / Q000096:biosynthesis*; D002454:Cell Differentiation / Q000187:drug effects*; D004785:Environmental Pollutants / Q000633:toxicity*; D051379:Mice; D000072317:Polychlorinated Dibenzodioxins / Q000633:toxicity*; D012333:RNA, Messenger / Q000032:analysis; D018336:Receptors, Aryl Hydrocarbon / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013755:Tetradecanoylphorbol Acetate / Q000633:toxicity; D014162:Transfection; D014409:Tumor Necrosis Factor-alpha / Q000633:toxicity
chemical_list: D022782:CCAAT-Enhancer-Binding Protein-beta; D004785:Environmental Pollutants; D000072317:Polychlorinated Dibenzodioxins; D012333:RNA, Messenger; D018336:Receptors, Aryl Hydrocarbon; D014409:Tumor Necrosis Factor-alpha; D013755:Tetradecanoylphorbol Acetate