Site‐selective 8‐chloroadenosine 3′,5′‐cyclic monophosphate inhibits transformation and transforming growth factor α production in Ki‐ras‐transformed rat fibroblasts

FEBS Letters

Clair, Timothy¹  Ciardiello, Fortunato¹  Salomon, David S.¹  Ally, Shamsia¹  Cho-Chung, Yoon Sang¹  Tortora, Giampaolo¹ 

[1] Laboratory of Tumor Immunology and Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA

关键词: cyclic AMP receptor protein;    Nuclear translocation;    Reverse transformation;    Protein;    p21ras;    cAMP;    cyclic adenosine 3′;    5′-monophosphate;    8-Cl-cAMP;    8-chloroadenosine 3′;    5′-cyclic monophosphate;    TGFα;    transforming growth factor α;    NRK;    normal rat kidney;    K-NRK;    Ki-ras-transformed NRK;    DMEM;    Dulbecco's modified Eaglemedium;    FBS;    fetal bovine serum;    RIA;    radioimmunoassay;    RRA;    radioreceptor assay;    EGF;    epidermal growth factor;   

DOI  :  10.1016/0014-5793(89)80502-2

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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.

【 授权许可】

Unknown