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

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 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.

• Authors: Gil Hong Park, Jaegol Choe, Hyo-Jung Choo, Yun Gyu Park, Jeongwon Sohn, Meyoung-kon Kim
• Journal: Experimental & molecular medicine (Exp Mol Med) Vol. 34 Issue 3 Pg. 184-93 (Jul 31 2002) ISSN: 1226-3613 [Print] United States
• PMID: 12216110 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• 2-Chloroadenosine
• 8-Bromo Cyclic Adenosine Monophosphate
• 8-chloro-cyclic adenosine monophosphate
• 8-chloroadenosine

Topics

• 2-Chloroadenosine (analogs & derivatives, chemistry, pharmacology)
• 8-Bromo Cyclic Adenosine Monophosphate (analogs & derivatives, chemistry, pharmacology)
• Antineoplastic Agents (chemistry, 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)