Site-selective 8-chloroadenosine 3',5'-cyclic monophosphate inhibits transformation and transforming growth factor alpha production in Ki-ras-transformed rat fibroblasts.
A site-selective cAMP analog, 8-chloroadenosine 3',5'-cyclic monophosphate (8-Cl-cAMP), was demonstrated to be a potent inhibitor of both the monolayer and soft agar growth of normal rat kidney (NRK) fibroblasts that had been transformed with the v-Ki-ras oncogene or treated with transforming growth factor alpha (TGF alpha). The growth inhibition was dose dependent and reversible and was accompanied by reversion of the transformed phenotype, suppression of TGF alpha production, and a decrease in p21 ras protein levels. These effects of 8-Cl-cAMP were linked to the cAMP analog's selective modulation of the type I and type II cAMP-dependent protein kinase regulatory subunits, RI and RII, present in Ki-ras-transformed and TGF alpha-treated NRK cells.
Tortora
G
G
Laboratory of Tumor Immunology and Biology, National Cancer Institute, Bethesda, MD 20892.
Ciardiello
F
F
Ally
S
S
Clair
T
T
Salomon
D S
DS
Cho-Chung
Y S
YS
D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D000970:Antineoplastic Agents; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002472:Cell Transformation, Viral / Q000187:drug effects*; D000242:Cyclic AMP / Q000031:analogs & derivatives*; D005786:Gene Expression Regulation / Q000187:drug effects; D011905:Genes, ras; D066298:In Vitro Techniques; D011494:Protein Kinases / Q000378:metabolism; D051381:Rats; D011953:Receptors, Cyclic AMP / Q000378:metabolism; D015291:Transforming Growth Factors / Q000096:biosynthesis*
D000970:Antineoplastic Agents; D011953:Receptors, Cyclic AMP; D015124:8-Bromo Cyclic Adenosine Monophosphate; D015291:Transforming Growth Factors; C044258:8-chloro-cyclic adenosine monophosphate; D000242:Cyclic AMP; D011494:Protein Kinases