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Site‐selective 8‐chloroadenosine 3′,5′‐cyclic monophosphate inhibits transformation and transforming growth factor α production in Ki‐ ras ‐transformed rat fibroblasts
Author(s) -
Tortora Giampaolo,
Ciardiello Fortunato,
Ally Shamsia,
Clair Timothy,
Salomon David S.,
Cho-Chung Yoon Sang
Publication year - 1989
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/0014-5793(89)80502-2
Subject(s) - transforming growth factor , chemistry , protein kinase a , growth factor , reversion , microbiology and biotechnology , alpha (finance) , transformation (genetics) , kinase , endocrinology , biology , medicine , receptor , phenotype , biochemistry , gene , construct validity , nursing , patient satisfaction
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 α (TGFα). The growth inhibition was dose dependent and reversible and was accompanied by reversion of the transformed phenotype, suppression of TGFα production, and a decrease in p21ras 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 TGFα‐treated NRK cells.