Inhibition of focal adhesion kinase by antisense oligonucleotides enhances the sensitivity of breast cancer cells to camptothecins
Biocell
;
27(1): 47-55, Apr. 2003.
Artículo
en Inglés
| LILACS
| ID: lil-384251
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:
Disponible
Índice:
LILACS (Américas)
Asunto principal:
Proteínas Tirosina Quinasas
/
Neoplasias de la Mama
/
Camptotecina
/
Oligonucleótidos Antisentido
/
Antineoplásicos Fitogénicos
Tipo de estudio:
Estudio diagnóstico
Límite:
Femenino
/
Humanos
Idioma:
Inglés
Revista:
Biocell
Asunto de la revista:
Clulas
Año:
2003
Tipo del documento:
Artículo
País de afiliación:
Estados Unidos
Institución/País de afiliación:
Barry University/US
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