Cho-Chung Y S, Clair T, Tagliaferri P, Ally S, Katsaros D, Tortora G, Neckers L, Avery T L, Crabtree G W, Robins R K
Cellular Biochemistry Section, National Cancer Institute, Bethesda, Maryland 20892.
Cancer Invest. 1989;7(2):161-77. doi: 10.3109/07357908909038282.
The physiologic role of cyclic adenosine monophosphate (cAMP) in the growth control of a spectrum of human cancer lines, including leukemic lines, and v-rasH oncogene-transformed NIH/3T3 cells is demonstrated by the use of site-selective cAMP analogs. These cAMP analogs, which can select either of the two known cAMP binding sites of the cAMP receptor protein, induce potent growth inhibition, phenotypic change, and differentiation (leukemic cells) of cancer cells at micromolar concentrations with no sign of cytotoxicity. The growth inhibition parallels selective modulation of cAMP-dependent protein kinase isozymes, type I versus type II, and suppression of cellular proto-oncogene expression. Site-selective cAMP analogs thus provide new biological tools for investigating cell proliferation and differentiation and also for the improved management of human cancers.
通过使用位点选择性环磷酸腺苷（cAMP）类似物，证明了cAMP在包括白血病细胞系在内的一系列人类癌细胞系以及v-rasH癌基因转化的NIH/3T3细胞生长控制中的生理作用。这些cAMP类似物可以选择cAMP受体蛋白的两个已知cAMP结合位点中的任何一个，在微摩尔浓度下即可诱导癌细胞产生强大的生长抑制、表型改变和分化（白血病细胞），且无细胞毒性迹象。生长抑制与cAMP依赖性蛋白激酶同工酶（I型与II型）的选择性调节以及细胞原癌基因表达的抑制平行。因此，位点选择性cAMP类似物为研究细胞增殖和分化以及改善人类癌症的治疗提供了新的生物学工具。
