Site‐selective 8‐C1‐cAMP which causes growth inhibition and differentiation increases DNA (CRE)‐binding activity in cancer cells

FEBS Letters

Clair, Timothy²  Mednieks, Maija I.³  Ally, Shamsia²  Yokozaki, Hiroshi²  Cho-Chung, Yoon Sang²  Merlo, Giorgio R.⁴  Tahara, Eiichi¹  Tortora, Giampaolo² 

[1] Department of Pathology, Hiroshima University School of Medicine, Hiroshima 734, Japan;the Cellular Biochemistry Section, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA;Department of Pediatrics, Section of Pediatric Endocrinology, Pritzker School of Medicine, University of Chicago, Chicago, IL 60637, USA;the Oncogenetics Section, Laboratory of Tumor Immunology and Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA

关键词: Gel retardation;    Transcription factor;    cyclic AMP responsiveness;    CRE;    cAMP-responsive element;    RIIβ;    type II cAMP-dependent protein kinase regulatory subunit;   

DOI  :  10.1016/0014-5793(89)81014-2

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Control mechanisms of normal differentiation are disrupted in cancer cells but can be restored by treatment with site-selective cAMP analogs. The cellular events associated with such changes entail compartmental redistribution of the cAMP-dependent protein kinase type II regulatory subunit, RII_β. The results of this study indicate that the molecular mechanisms of action involve changes in specific DNA-binding activity of putative transcription factors. Gel retardation analyses revealed that nuclear extracts from cells of various human cancer cell lines [colon cancer (LS-174T), gastric cancer (TMK-1), and leukemia (K-562)] and rodent pheochromocytoma (PC12) show a concentration-dependent increase in binding activity to a synthetic DNA that contained the cAMP-responsive element 5′-TGACGTCA-3′ after treatment with 8-C1-cAMP. Such an increase in cAMP-responsive element binding activity was not observed in the 8-C1-cAMP-unresponsive MKN-1 gastric cancer cells. These findings indicate that the antitumor activity of site-selective cAMP analogs may reside in the induction of transcription factors that restore normal gene regulation in cancer cells.

【 授权许可】

Unknown