The effect of tumor-promoting phorbol diesters on terminal differentiation of cells in culture.
The effect of tumor-promoting phorbol diesters on terminal differentiation of cells in culture.
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促肿瘤佛波二酯对培养细胞终末分化的影响。
DOI：
10.1007/bf00225849
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发表时间：
1980
影响因子：
4.3
通讯作者：
Rovera,G
中科院分区：
文献类型：
--
作者：
Abrahm,J;Rovera,G
具有促肿瘤活性的佛波醇二酯，特别是12-0-十四烷酰基-佛波醇-13-乙酸酯（TPA），可以诱导或抑制多种细胞系统的终末分化，对特定细胞谱系具有特异性。荧光素酶是研究某些细胞中分化的表达和控制以及致癌剂干扰终末分化过程的机制的极好工具。目前还不清楚佛波酯对不同靶细胞的作用机制。认为细胞的状态是非常重要的，因为在某些情况下，使用相同浓度的佛波醇二酯可以获得相反的效果。细胞膜、受体的变化、胰高血糖素的分泌和环磷酸腺苷水平的变化都有报道。然而，这些变化与分化过程中所涉及的遗传程序的改变之间的关系尚不清楚，最近关于佛波醇二酯可能的细胞受体的报道应阐明其作用机制。佛波醇二酯对分化的影响的研究结果表明，促进可以通过抑制细胞分化介导的可验证的假设。也有人认为，分化系统的变化可能是未来用于筛选未知的肿瘤促进剂，然而，这种可能性似乎相当遥远。最后，具有肿瘤促进活性的佛波醇二酯似乎对小鼠和人类来源的白血病细胞的分化产生特定的影响，因此，这种特殊现象在实验治疗中的应用应该是未来研究的主题。
Phorbol diesters with tumor-promoting activity, in particular, 12-0-tetradecanoyl-phorbol-13-acetate (TPA), can induce or inhibit terminal differentiation in a variety of cell systems, with specificity for particular cell lineages. The phorbols are excellent tools to investigate the expression and control of differentiation in some cells and the mechanism by which oncogenic agents interfere with the process of terminal differentiation. The mechanism of action of the phorbols on different target cells is not understood at the present time. It is felt that the status of the cell is of major importance as, in some cases, opposite effects can be achieved by the same concentration of the phorbol diester used. Changes in membranes, receptors, in secretion of prostaglandins and in the level of cyclic AMP have all been reported. However, the relationship of these changes with the alterations in the genetic program involved in the differentiation process is not clear, and the recent report of a possible cell receptor for phorbol diesters should elucidate their mechanism of action. The findings on the effect of phorbol diesters on differentiation have suggested the testable hypothesis that promotion could be mediated through inhibition of cellular differentiation. It has also been suggested that changes in differentiating systems could be of future use in screening for unknown tumor promoters, however, this possibility seems quite remote. Finally, phorbol diesters with tumor-promoting activity appear to exert a specific effect on differentiation of leukemic cells of both mouse and human origin, and therefore, the application of this particular phenomenon in experimental therapy should be the subject of future investigations.