Apoptosis, growth arrest and suppression of invasiveness by CRE-decoy oligonucleotide in ovarian cancer cells: protein kinase A downregulation and cytoplasmic export of CRE-binding proteins.
Mol Cell Biochem
; 218(1-2): 55-63, 2001 Feb.
Article
em En
| MEDLINE
| ID: mdl-11330838
ABSTRACT
The CRE (cyclic AMP response element)-transcription factor complex plays a critical role in response to hormonal signals for cell proliferation, differentiation, and apoptosis. We have reported previously that the CRE-transcription factor decoy oligonucleotide specifically slows tumor cell proliferation and inhibits CRE- and Ap-1-directed transcription in vivo (Park et al., 1999). We have investigated the effect of inhibiting CRE-directed transcription on ovarian cancer cell growth. Here, we report that CRE-decoy oligonucleotide treatment results in the inhibition of cell growth and a marked reduction in the expression of the regulatory and catalytic subunits of protein kinase A and the type I and type II protein kinase A holoenzymes. Growth inhibition was accompanied by changes in cell morphology, appearance of apoptotic nuclei, and DNA fragmentation. In addition, MMP-9 (matrix methalloproteinase-9) activity was markedly reduced in CRE-decoy treated cells. Indirect immunofluorescence revealed that CRE-decoy oligonucleotide treatment promoted export of the CRE-binding protein, CREB, from the nucleus to the cytoplasm, while importing the catalytic subunit of protein kinase A from the cytoplasm to the nucleus. The results indicate that the decoy oligonucleotide, by binding specifically to CRE-transcription factors, interferes with CRE-directed transcription in vivo. These results show a critical role for CRE-directed transcription in ovarian cancer cell growth. Thus, the CRE-decoy oligonucleotide may provide a powerful means to combat ovarian cancer.
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Coleções:
01-internacional
Contexto em Saúde:
6_ODS3_enfermedades_notrasmisibles
Base de dados:
MEDLINE
Assunto principal:
Neoplasias Ovarianas
/
Divisão Celular
/
Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico
/
Apoptose
/
Proteínas Quinases Dependentes de AMP Cíclico
/
Fator de Transcrição AP-1
Limite:
Female
/
Humans
Idioma:
En
Revista:
Mol Cell Biochem
Ano de publicação:
2001
Tipo de documento:
Article