[Specific induction by phorbol ester of the gene transcription and of the activity of ornithine decarboxylase in two control and transformed epithelial cell lines. Modulator effect of anti-inflammatory agents].
The mechanism of ornithine decarboxylase (ODC) induction by phorbol ester (TPA) has been studied in two permanent epithelial cell lines, a control (Ctr) and a Benzo (a) pyrene transformed line (BaP-tr); the degree of ODC gene expression (ODC-mRNA) was evaluated in comparison to the ODC activity. A small dose of TPA (4 x 10(-8) M) highly induced ODC activity in these cells. The induction levels differed however, corresponding respectively to 4:1 (induced: basal ODC) in Ctr cells and to 2:1 in BaP-tr cells. This difference reflected the variation of ODC gene expression; the ODC-mRNA induction was 6:1 in Ctr cells and 3:1 in BaP-tr cells. Repetitive TPA treatment decreased the ODC induction in these cells, as compared to that resulting from a single TPA treatment. Studies of ODC modulation were performed in presence of anti-inflammatory agents. In the two cell lines, Indomethacin (anti-cyclooxygenase) did not change the level of ODC induction by TPA. Nordihydroguaiaretic acid (NDGA, anti-lipoxygenase) inhibited this induced ODC. These results differed from that obtained in vivo in mouse skin. Dexamethasone (DXME, anti-phospholipase A2) showed different action according to treatment time. Used together with TPA (t0), DXME inhibited ODC induction by the carcinogen; with three hours delay after TPA (t3), DXME treatment stimulated ODC in the cells. This divergent action may be reproduced by Actinomycin D, while Cycloheximide only exhibited constant inhibition. Studies now in progress suggested that the inhibition of TPA induced ODC by DXME may reflect ODC gene repression, as for the stimulating effect it could be related to ODC post-transcriptional modulation, owing to the decrease of proteolytic action.
Nguyen-Ba
G
G
Laboratoire de Pharmacologie Cellulaire, I.C.I.G., Villejuif.
Robert
S
S
Lasne
C
C
Ventura
L
L
Chouroulinkov
I
I
van Kreijl
C F
CF
van Steeg
H
H
Truhaut
R
R
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002460:Cell Line; D002461:Cell Line, Transformed; D004847:Epithelial Cells; D004848:Epithelium / Q000201:enzymology; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D009955:Ornithine Decarboxylase / Q000235:genetics* / Q000378:metabolism; D051381:Rats; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D014158:Transcription, Genetic / Q000187:drug effects*
D000893:Anti-Inflammatory Agents; D009955:Ornithine Decarboxylase; D013755:Tetradecanoylphorbol Acetate
Induction spécifique par l'ester de phorbol de la transcription du gène et de l'activité d'ornithine décarboxylase dans deux lignées de cellules épithéliales témoins et transformées. Effet modulateur des agents anti-inflammatoires.