Abstract
The retinoblastoma protein-interacting zinc finger gene RIZ1 is a tumor suppressor gene and a member of a nuclear histone/protein methyltransferase superfamily. RIZ1 inactivation is commonly found in many types of human cancers and occurs through loss of mRNA expression, frameshift mutation, chromosomal deletion, and missense mutation. RIZ1 is also a tumor susceptibility gene in mice. We now show that loss of RIZ1 mRNA in human cancers is associated with DNA methylation of its promoter CpG island. Methylation of the RIZ1 promoter strongly correlated with lost or decreased RIZ1 mRNA expression in breast, liver, colon, and lung cancer cell lines as well as in liver cancer tissues. Treatment with the methylation inhibitor 5-aza-2'-deoxycytidine activated RIZ1 mRNA expression in cancer cells. Furthermore, methylation was found in 11 of 25 (44%) breast cancer specimens and 20 of 32 (62%) liver cancer specimens. Our results suggest that DNA methylation is a common mechanism in inactivating the RIZ1 tumor suppressor gene in human liver and breast cancers.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Azacitidine / analogs & derivatives*
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Azacitidine / pharmacology
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Base Sequence
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Cloning, Molecular
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CpG Islands / genetics
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DNA Methylation*
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DNA, Neoplasm / genetics
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DNA-Binding Proteins*
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Decitabine
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Enzyme Inhibitors / pharmacology
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Gene Expression Regulation, Neoplastic
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Gene Silencing
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Genes, Tumor Suppressor*
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Histone Methyltransferases
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Histone-Lysine N-Methyltransferase*
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Humans
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Methyltransferases / biosynthesis
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Methyltransferases / genetics*
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Molecular Sequence Data
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Neoplasms / enzymology
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Neoplasms / genetics*
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Neoplasms / metabolism
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Nuclear Proteins / biosynthesis
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Nuclear Proteins / genetics*
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Promoter Regions, Genetic
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Protein Methyltransferases
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RNA, Messenger / biosynthesis
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RNA, Messenger / genetics
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Rats
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Retinoblastoma Protein / genetics
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Retinoblastoma Protein / metabolism
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Transcription Factors*
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Zinc Fingers / genetics
Substances
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DNA, Neoplasm
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DNA-Binding Proteins
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Enzyme Inhibitors
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Nuclear Proteins
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RNA, Messenger
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Retinoblastoma Protein
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Transcription Factors
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Decitabine
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Histone Methyltransferases
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Methyltransferases
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Protein Methyltransferases
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Histone-Lysine N-Methyltransferase
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PRDM2 protein, human
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Azacitidine