Role of activator protein-1 and methylation function in 12-O-tetradecanoylphorbol-13-acetate--mediated inhibition of differentiation of Friend erythroleukemia cells.
Friend erythroleukemia cells (FELCs) differentiate after hexamethylene-bis-acetamide treatment. This differentiation is characterized by an increase in beta-globin gene expression that is followed by appearance of the hemoglobin. Phorbol-ester tumor promoters, such as 12-O-tetradecanoylphorbol-13-acetate (TPA), inhibit differentiation of TPA-sensitive cells but not TPA-resistant cells. We have shown that the increase in beta-globin expression is inhibited by TPA in a TPA-sensitive clone but not in a TPA-resistant clone. To study the molecular mechanisms of regulation of gene expression by TPA, we examined the possible involvement of gene methylation and the TPA-responsive element (TRE). Both clones showed similar patterns of methylation around the beta-globin gene. Moreover, TPA-induced TRE binding and TRE enhancer activity were similar in both variants. These results suggest that the TPA inhibition of induced differentiation may not be explained by regulation of the methylation state. The activator protein-1 also does not play a crucial role in the sensitivity of FELCs to TPA.
Bertrand
O
O
International Agency for Research on Cancer, Lyon, France.
Giroldi
L
L
Nakazawa
H
H
Sergeant
A
A
Yamasaki
H
H
D000818:Animals; D001483:Base Sequence; D002454:Cell Differentiation / Q000187:drug effects; D004591:Electrophoresis, Polyacrylamide Gel; D005622:Friend murine leukemia virus; D005786:Gene Expression Regulation / Q000187:drug effects*; D005914:Globins / Q000096:biosynthesis / Q000235:genetics; D004915:Leukemia, Erythroblastic, Acute / Q000473:pathology*; D008745:Methylation / Q000187:drug effects; D051379:Mice; D008969:Molecular Sequence Data; D016755:Proto-Oncogene Proteins c-jun / Q000502:physiology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D015533:Transcriptional Activation / Q000187:drug effects; D014162:Transfection; D014407:Tumor Cells, Cultured
D016755:Proto-Oncogene Proteins c-jun; D005914:Globins; D013755:Tetradecanoylphorbol Acetate