RIZ Gene in Human Breast Cancer

摘要

The retinoblastoma protein-interacting zinc finger gene RIZ maps to the distal short arm of human chromosome I (1p36), a region thought to harbor tumor suppressor genes for a variety of human cancers including breast cancer. The RIZ gene normally produces two protein products of different length, RIZ1 and RIZ2. RIZ2 is generated by an internal promoter and lacks an amino-terminal motif of RIZ 1, the PR domain conserved in a sub-family of zinc finger genes which function as negative regulators of tumorigenesis. We have here studied whether the MZ gene may play a role in human breast cancer. We found that expression of RIZ 1 is commonly decreased or at undetectable levels in breast cancer tissues and cell lines. Decreased RIZ 1 expression was also found in other tumor types including neuroblastoma and lung cancer. Remarkably, RIZ2 is normally expressed in all cases examined, suggesting that the abnormality observed for RIZ 1 is specific. Forced RIZ 1 expression in breast cancer cells caused cell cycle arrest in G2/M and/or programmed cell death. These observations suggest an exclusive negative selection for RIZ 1 but not RIZ2 in breast cancer and a role for RIZ 1 in tumor suppression.