Site-selective cyclic AMP analogs as new biological tools in growth control, differentiation, and proto-oncogene regulation.
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.
Cho-Chung
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Cellular Biochemistry Section, National Cancer Institute, Bethesda, Maryland 20892.
Clair
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Tagliaferri
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Ally
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Katsaros
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Tortora
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Neckers
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Avery
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Crabtree
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Robins
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D000818:Animals; D001665:Binding Sites; D002454:Cell Differentiation; D002455:Cell Division; D000242:Cyclic AMP / Q000031:analogs & derivatives*; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D000090063:Proto-Oncogene Mas; D011519:Proto-Oncogenes / Q000187:drug effects*; D011953:Receptors, Cyclic AMP / Q000187:drug effects; D014407:Tumor Cells, Cultured / Q000187:drug effects*
C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D011953:Receptors, Cyclic AMP; D000242:Cyclic AMP