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

The distal short arm of human chromosome I (1p36) is commonly altered in pr imary 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 transc ription factors. An unusual feature of this family is the yin-yang involvem ent in human cancers. Two products are normally produced from a PR family m ember 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 pre sent or overexpressed in cancer cells. The PR-plus product RIZ1 is a candid ate tumor suppressor because it can induce G(2)/M arrest and/or apoptosis a nd is commonly underexpressed in breast cancer. Here, we have investigated the role of RIZ in hepatoma. RIZ1 transcript was undetectable in 80% of hep atoma cell lines (8 of 10 lines examined). RIZ1 expression was also decreas ed in hepatoma tumor specimens. In contrast, RIZ2 transcript was uniformly present in all samples examined. Adenovirus-mediated RIZ1 expression in hep atoma 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 produ cts in human cancer and suggest a RIZ1 tumor suppressor role in hepatoma, I nt J. Cancer 83:541-546, 1999. (C) 1999 Wiley-Liss, Inc.