Decreased RIZ1 expression but not RIZ2 in hepatoma and suppression of hepatoma tumorigenicity by RIZ1.
The distal short arm of human chromosome 1 (1p36) is commonly altered in primary hepatoma tumors and cell lines. This region includes the RIZ gene, a member of the PR (PRDI-BF1/BLIMP1 and RIZ homology) domain family of transcription factors. An unusual feature of this family is the yin-yang involvement in human cancers. Two products are normally produced from a PR family member which differ by the presence or absence of the PR domain; the PR-plus product is disrupted or underexpressed whereas the PR-minus product is present or overexpressed in cancer cells. The PR-plus product RIZ1 is a candidate tumor suppressor because it can induce G(2)/M arrest and/or apoptosis and is commonly underexpressed in breast cancer. Here, we have investigated the role of RIZ in hepatoma. RIZ1 transcript was undetectable in 80% of hepatoma cell lines (8 of 10 lines examined). RIZ1 expression was also decreased in hepatoma tumor specimens. In contrast, RIZ2 transcript was uniformly present in all samples examined. Adenovirus-mediated RIZ1 expression in hepatoma cell lines caused cell cycle arrest in G(2)/M and/or programmed cell death. RIZ1 expression also suppressed tumorigenicity of hepatoma cells in nude mice. Our observations reinforce the yin-yang notion of RIZ gene products in human cancer and suggest a RIZ1 tumor suppressor role in hepatoma.
Jiang
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Program in Oncogenes and Tumor Suppressor Genes, The Burnham Institute, La Jolla, California 92037, USA.
Liu
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Buyse
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Simon
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Huang
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D000818:Animals; D017209:Apoptosis; D006528:Carcinoma, Hepatocellular / Q000378:metabolism* / Q000473:pathology; D002453:Cell Cycle / Q000235:genetics; D002455:Cell Division / Q000235:genetics; D004247:DNA / Q000378:metabolism; D004268:DNA-Binding Proteins; D011495:Histone-Lysine N-Methyltransferase; D006801:Humans; D015151:Immunoblotting; D008113:Liver Neoplasms / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009687:Nuclear Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D012333:RNA, Messenger / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D014157:Transcription Factors; D014162:Transfection; D014407:Tumor Cells, Cultured
D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D012333:RNA, Messenger; D014157:Transcription Factors; D004247:DNA; D011495:Histone-Lysine N-Methyltransferase; C093563:PRDM2 protein, human