Suppression of malignancy targeting the intracellular signal transducing proteins of cAMP: the use of site-selective cAMP analogs, antisense strategy, and gene transfer.
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.
Cho-Chung
Y S
YS
Cellular Biochemistry Section, National Cancer Institute, Bethesda, Maryland 20892.
Clair
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T
Tortora
G
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Yokozaki
H
H
Pepe
S
S
D000818:Animals; D016375:Antisense Elements (Genetics); D000242:Cyclic AMP / Q000031:analogs & derivatives / Q000502:physiology; D006801:Humans; D007424:Intracellular Fluid / Q000502:physiology; D009369:Neoplasms / Q000188:drug therapy* / Q000209:etiology / Q000235:genetics / Q000473:pathology; D011953:Receptors, Cyclic AMP / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*; D014162:Transfection / Q000235:genetics; D014407:Tumor Cells, Cultured
D016375:Antisense Elements (Genetics); D011953:Receptors, Cyclic AMP; D000242:Cyclic AMP