Microarray analysis of gene expression in metastatic gastric cancer cells after incubation with the methylation inhibitor 5-aza-2'-deoxycytidine.
While the exact mechanisms involved in cancer metastasis are not fully clarified, the altered expression of many different genes has been reported. Hypermethylation of the promoters of cancer-related genes is often associated with their inactivation during tumorigenesis and may also be involved in metastasis. Here we used cDNA microarrays to examine the different gene expression profiles of a primary gastric adenocarcinoma cell line RF1 and its derivative metastasis subline RF48. Compared with RF1, 49 genes were down-regulated and 8 genes were up-regulated in RF48. After treatment of RF48 cells with a DNA methylation inhibitor, 5-aza-2'-deoxycytidine, 101 genes were up-regulated and 1 gene was down-regulated in treated RF48 when compared with untreated RF48. Comparing gene expression patterns of untreated RF1, untreated RF48 and treated RF48 cells showed 5 genes expressed in RF1 but silenced in RF48, which were reactivated after 5-aza-2'-deoxycytidine treatment. Two of those 5 genes have CpG islands within their promoter regions, suggesting that those genes activated by 5-aza-2'-deoxycytidine may result from the direct inhibition of promoter methylation. In conclusion, using global gene expression analysis together with inhibition of DNA methylation, we demonstrate that hypermethylation of the promoters of certain cancer-related genes may play a role in cancer metastasis.
Chen
Jie
J
Department of Gastroenterology, Hepatology and Infectious Diseases, Otto-von-Guericke University, Magdeburg 39120, Germany.
Röcken
Christoph
C
Klein-Hitpass
Ludger
L
Götze
Tobias
T
Leodolter
Andreas
A
Malfertheiner
Peter
P
Ebert
Matthias P A
MP
D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism / Q000556:secondary; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology*; D001374:Azacitidine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D018899:CpG Islands; D019175:DNA Methylation / Q000187:drug effects*; D000077209:Decitabine; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D020868:Gene Silencing; D006801:Humans; D009363:Neoplasm Proteins / Q000235:genetics* / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D011401:Promoter Regions, Genetic; D013274:Stomach Neoplasms / Q000235:genetics* / Q000378:metabolism; D014407:Tumor Cells, Cultured
D000964:Antimetabolites, Antineoplastic; D009363:Neoplasm Proteins; D000077209:Decitabine; D001374:Azacitidine