Inhibition of growth of mouse gastric cancer cells by Runx3, a novel tumor suppressor.
We reported recently that the silencing of RUNX3 is causally related to gastric cancer in humans. Here we report that in three of four cell lines derived from N-methyl-N-nitrosourea-induced mouse glandular stomach carcinomas, Runx3 is silenced due to hypermethylation of CpG islands in the promoter region, as we also observed for human gastric cancer cells. Although two of the sites we tested in the promoter of the fourth line were not methylated, in all four cases the silencing of Runx3 could be reversed by treatment of the cells with 5'-azacytidine and trichostatin A. Interestingly, the exogenous expression of RUNX3 in cell lines that do not express the endogenous gene caused an inhibition of growth in soft agar, suggesting that anchorage-independent growth could be used as an assay of RUNX3 activity in vitro. These observations suggest that the mouse system described here may be useful as a model for the study of human gastric carcinogenesis.
Guo
Wei-Hui
WH
Department of Viral Oncology, Institute for Virus Research, Kyoto University, Shogoin, Sakyo-ku Kyoto 606-8507, Japan.
Weng
Li-Qin
LQ
Ito
Kosei
K
Chen
Lin-Feng
LF
Nakanishi
Hayao
H
Tatematsu
Masae
M
Ito
Yoshiaki
Y
D000818:Animals; D001374:Azacitidine / Q000494:pharmacology; D001483:Base Sequence; D002455:Cell Division / Q000235:genetics*; D050677:Core Binding Factor Alpha 3 Subunit; D018899:CpG Islands; D019175:DNA Methylation; D004273:DNA, Neoplasm; D004268:DNA-Binding Proteins / Q000235:genetics*; D020868:Gene Silencing / Q000187:drug effects; D016147:Genes, Tumor Suppressor; D006877:Hydroxamic Acids / Q000494:pharmacology; D051379:Mice; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics; D013274:Stomach Neoplasms / Q000235:genetics / Q000473:pathology*; D014157:Transcription Factors / Q000235:genetics*
D050677:Core Binding Factor Alpha 3 Subunit; D004273:DNA, Neoplasm; D004268:DNA-Binding Proteins; D006877:Hydroxamic Acids; D012333:RNA, Messenger; C493730:Runx3 protein, mouse; D014157:Transcription Factors; C012589:trichostatin A; D001374:Azacitidine