Site-selective 8-Cl-cAMP which causes growth inhibition and differentiation increases DNA (CRE)-binding activity in cancer cells.
FEBS Lett
; 254(1-2): 83-8, 1989 Aug 28.
Article
em En
| MEDLINE
| ID: mdl-2528474
ABSTRACT
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 beta. 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-Cl-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.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Transcrição Gênica
/
8-Bromo Monofosfato de Adenosina Cíclica
/
DNA de Neoplasias
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Células Tumorais Cultivadas
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Diferenciação Celular
/
Divisão Celular
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Proteínas de Ligação a DNA
/
Antineoplásicos
Tipo de estudo:
Etiology_studies
Limite:
Animals
/
Humans
Idioma:
En
Revista:
FEBS Lett
Ano de publicação:
1989
Tipo de documento:
Article