Butler A P, Mar P K, McDonald F F, Ramsay R L
University of Texas M.D. Anderson Cancer Center, Department of Carcinogenesis, Smithville 78957.
Exp Cell Res. 1991 May;194(1):56-61. doi: 10.1016/0014-4827(91)90129-i.
The tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) stimulates a rapid increase in ornithine decarboxylase (EC 4.1.1.17; ODC) activity in target cells. Here we demonstrate that this process involves a rapid accumulation of ODC mRNA, which is maximal 3 h after treatment (three- to eightfold greater than control cells) and decays to control levels within 18 h. Stimulation of ODC mRNA by TPA is blocked by phorbol dibutyrate down-regulation of protein kinase C (PKC). ODC mRNA was also induced by the PKC activators, phospholipase C and 1-oleoyl-2-acetyl-rac-glycerol, and blocked by kinase inhibitors (trifluoroperazine, H7, and palmitoyl-L-carnitine), consistent with a requirement for PKC activation in the induction mechanism. However, the non-PKC-specific protein kinase inhibitor HA1004 also suppressed expression of ODC mRNA in response to TPA, under conditions where it did not inhibit PKC, suggesting that additional kinases may be involved in the intracellular signalling process. The stability of the ODC mRNA (control value = 6.2 +/- 1.6 h) is not significantly changed by either TPA (5.7 +/- 0.8 h) or by cycloheximide (6.0 h). These results are inconsistent with any contribution from altered mRNA half-life towards the accumulation of ODC mRNA following treatment with phorbol ester tumor promoters.
肿瘤促进剂12 - O - 十四烷酰佛波醇 - 13 - 乙酸酯（TPA）可刺激靶细胞中鸟氨酸脱羧酶（EC 4.1.1.17；ODC）活性迅速增加。在此我们证明，这一过程涉及ODC mRNA的快速积累，在处理后3小时达到最大值（比对照细胞高3至8倍），并在18小时内衰减至对照水平。TPA对ODC mRNA的刺激可被佛波醇二丁酸酯下调蛋白激酶C（PKC）所阻断。ODC mRNA也可被PKC激活剂磷脂酶C和1 - 油酰 - 2 - 乙酰 - rac - 甘油诱导，并被激酶抑制剂（三氟拉嗪、H7和棕榈酰 - L - 肉碱）阻断，这与诱导机制中PKC激活的需求一致。然而，非PKC特异性蛋白激酶抑制剂HA1004在不抑制PKC的条件下，也能抑制TPA诱导的ODC mRNA表达，这表明可能有其他激酶参与细胞内信号传导过程。TPA（5.7 +/- 0.8小时）或环己酰亚胺（6.0小时）对ODC mRNA的稳定性（对照值 = 6.2 +/- 1.6小时）均无显著影响。这些结果与佛波酯肿瘤促进剂处理后ODC mRNA积累过程中mRNA半衰期改变所起的任何作用均不相符。
