Inhibition of focal adhesion kinase by antisense oligonucleotides enhances the sensitivity of breast cancer cells to camptothecins
Biocell
; 27(1): 47-55, Apr. 2003.
Artigo
em Inglês
| LILACS
| ID: lil-384251
Biblioteca responsável:
BR1.1
RESUMO
This study shows a strong association between cell attachment to substratum and activation of beta 1-integrin-signaling with resistance to the camptothecin derivative topotecan (TPT) in breast cancer cells. We propose a mechanistic-driven approach to sensitize the cells to camptothecins. ZR-75-1 anchorage-dependent breast cancer cell line, its derivative 9D3S suspension cells (9D3S-S), and 9D3S cells attached to fibronectin-coated plates (9D3S-A) were treated with TPT (1 microM) or CPT-11 (40 microM) for 48 h. Programmed cell death (PCD), as shown by poly(ADP-ribose) polymerase (PARP), pro-caspase-3 and pro-caspase-9 cleavage, was observed in 9D3S-S cells but not in ZR-75-1 or 9D3S-A cells. Because p125 focal adhesion kinase (FAK) is a transducer in the beta 1-integrin signaling pathway, it is essential to cell adhesion and it is overexpressed in metastatic breast cancer, we hypothesized that attenuation of FAK might enhance the sensitivity of breast cancer cells to camptothecins. Moreover, inhibition of FAK gene expression by a phosphorothioated antisense oligodeoxynucleotide targeting the portion of the gene encoding amino acids 262-268, increased the sensitivity of ZR-75-1, MDA-MB-231 and MCF7 breast cancer cells to treatment with TPT or CPT-11.
Texto completo:
Disponível
Coleções:
Bases de dados internacionais
Base de dados:
LILACS
Assunto principal:
Proteínas Tirosina Quinases
/
Neoplasias da Mama
/
Camptotecina
/
Oligonucleotídeos Antissenso
/
Antineoplásicos Fitogênicos
Tipo de estudo:
Estudo diagnóstico
Limite:
Feminino
/
Humanos
Idioma:
Inglês
Revista:
Biocell
Assunto da revista:
Clulas
Ano de publicação:
2003
Tipo de documento:
Artigo
País de afiliação:
Estados Unidos
Instituição/País de afiliação:
Barry University/US