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.