Genome-wide expression profiling of 8-chloroadenosine- and 8-chloro-cAMP-treated human neuroblastoma cells using radioactive human cDNA microarray

• Published in: Experimental & molecular medicine 2002-07, Vol.34 (3), p.184-193
• Main Authors: Park, Gil Hong, Choe, Jaegol, Choo, Hyo-Jung, Park, Yun Gyu, Sohn, Jeongwon, Kim, Meyoung-kon
• Format: Article
• Language: English
• Subjects: 2-Chloroadenosine - analogs & derivatives; 2-Chloroadenosine - chemistry; 2-Chloroadenosine - pharmacology; 8-Bromo Cyclic Adenosine Monophosphate - analogs & derivatives; 8-Bromo Cyclic Adenosine Monophosphate - chemistry; 8-Bromo Cyclic Adenosine Monophosphate - pharmacology; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Blotting, Western; Gene Expression Profiling; Gene Expression Regulation, Neoplastic - drug effects; Genome, Human; Humans; Neuroblastoma - genetics; Oligonucleotide Array Sequence Analysis; Reproducibility of Results; Tumor Cells, Cultured; Up-Regulation - drug effects
• ISSN: 1226-3613; 2092-6413; 2092-6413
• DOI: 10.1038/emm.2002.27

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 systematically 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 (33)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-regulated 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.