Genome-wide expression profiling of 8-chloroadenosine- and 8-chloro-cAMP-treated human neuroblastoma cells using radioactive human cDNA microarray
Experimental & Molecular Medicine
;
: 184-193, 2002.
Artículo
en Inglés
| WPRIM
| ID: wpr-198794
ABSTRACT
Previous reports raised question as to whether 8-chloro-cyclic adenosine 3,5-monophosphate (8-Cl-cAMP) is a prodrug for its metabolite, 8-Cl-adenosine which exerts growth inhibition in a broad spectrum of cancer cells. The present study was carried out to clarify overall cellular affects of 8-Cl-cAMP and 8-Cl-adenosine on SK-N-DZ human neuroblastoma cells by ystematically characterizing gene expression using radioactive human cDNA microarray. Microarray was prepared with PCR-amplified cDNA of 2,304 known genes spotted on nylon membranes, employing (1)P-labeled cDNAs of SK-N-DZ cells as a probe. the expression levels of approximately 100 cDNAs, representing about 8% of the total DNA elements on the array, were altered in 8-Cl-adenosine- or 8-Cl-cAMP-treated cells, respectively. The genome-wide expression of the two samples exhibited partial overlaps; different sets of up-regulated genes but the same set of down-regulated genes. 8-Cl-adenosine treatment up- egulated genes involved in differentiation and development (LIM protein, connexin 26, neogenin, neurofilament triplet L protein and p21( WAF1/CIP1)) and immune response such as natural killer cells protein 4, and down-regulated ones involved in proliferation and transformation (transforming growth factor-beta, DYRK2, urokinase-type plasminogen activator and proteins involved in transcription and translation) which were in close parallel with those by 8-Cl-cAMP. Our results indicated that the two drugs shared common genomic pathways for the down-regulation of certain genes, but used distinct pathways for the up-regulation of different gene clusters. Based on the findings, we suggest that the anti-cancer activity of 8-Cl-cAMP results at least in part through 8-Cl-adenosine. Thus, the systematic use of DNA arrays can provide insight into the dynamic cellular pathways involved in anticancer activities of chemotherapeutics.
Texto completo:
Disponible
Índice:
WPRIM (Pacífico Occidental)
Asunto principal:
8-Bromo Monofosfato de Adenosina Cíclica
/
Células Tumorales Cultivadas
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2-Cloroadenosina
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Regulación Neoplásica de la Expresión Génica
/
Genoma Humano
/
Regulación hacia Arriba
/
Western Blotting
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Reproducibilidad de los Resultados
/
Análisis de Secuencia por Matrices de Oligonucleótidos
/
Perfilación de la Expresión Génica
Límite:
Humanos
Idioma:
Inglés
Revista:
Experimental & Molecular Medicine
Año:
2002
Tipo del documento:
Artículo
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