Decreased RIZ1 expression but not RIZ2 in hepatoma and suppression of hepatoma tumorigenicity by RIZ1

Int J Cancer. 1999 Nov 12;83(4):541-6. doi: 10.1002/(sici)1097-0215(19991112)83:4<541::aid-ijc17>;2-f.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Apoptosis
  • Carcinoma, Hepatocellular / metabolism*
  • Carcinoma, Hepatocellular / pathology
  • Cell Cycle / genetics
  • Cell Division / genetics
  • DNA / metabolism
  • DNA-Binding Proteins*
  • Histone-Lysine N-Methyltransferase
  • Humans
  • Immunoblotting
  • Liver Neoplasms / metabolism*
  • Liver Neoplasms / pathology
  • Mice
  • Mice, Nude
  • Neoplasm Transplantation
  • Nuclear Proteins / biosynthesis*
  • Nuclear Proteins / genetics
  • Nuclear Proteins / physiology
  • RNA, Messenger / biosynthesis
  • Reverse Transcriptase Polymerase Chain Reaction
  • Time Factors
  • Transcription Factors*
  • Transfection
  • Tumor Cells, Cultured


  • DNA-Binding Proteins
  • Nuclear Proteins
  • RNA, Messenger
  • Transcription Factors
  • DNA
  • Histone-Lysine N-Methyltransferase
  • PRDM2 protein, human