Cho-Chung Y S, Clair T, Tortora G, Yokozaki H, Pepe S
Cellular Biochemistry Section, National Cancer Institute, Bethesda, Maryland 20892.
Life Sci. 1991;48(12):1123-32. doi: 10.1016/0024-3205(91)90449-l.
An hypothesis has been presented suggesting that two isoforms of cAMP receptor proteins are crucial effectors in tumorigenesis. The evidence in support of this hypothesis shows that: (1) cAMP transduces dual controls, both positive and negative, on cell growth and differentiation. (2) Such dual controls are respectively governed by two isoforms of cAMP receptor proteins, the type I and type II regulatory subunits of cAMP-dependent protein kinase. (3) In normal physiology, the functional balance of these cAMP receptor isoforms is strictly controlled to meet either stimulation or inhibition of cell growth as it is required, whereas such control is lost in cancer cells. (4) Cancer cells can also be made to differentiate and acquire growth control when the functional balance of these intracellular signal transducers of cAMP is restored by the use of site-selective cAMP analogs, antisense strategy, or gene transfer, suggesting new approaches to cancer therapy.
一种假说认为，环磷酸腺苷（cAMP）受体蛋白的两种亚型是肿瘤发生的关键效应因子。支持这一假说的证据表明：（1）cAMP对细胞生长和分化具有正负双重调控作用。（2）这种双重调控分别由cAMP受体蛋白的两种亚型，即cAMP依赖性蛋白激酶的I型和II型调节亚基所控制。（3）在正常生理状态下，这些cAMP受体亚型的功能平衡受到严格控制，以根据需要对细胞生长进行刺激或抑制，而在癌细胞中这种控制则丧失。（4）当通过使用位点选择性cAMP类似物、反义策略或基因转移恢复这些cAMP细胞内信号转导子的功能平衡时，癌细胞也可发生分化并获得生长控制，这提示了癌症治疗的新方法。
