RIZ1, BUT NOT THE ALTERNATIVE RIZ2 PRODUCT OF THE SAME GENE, IS UNDEREXPRESSED IN BREAST-CANCER, AND FORCED RIZ1 EXPRESSION CAUSES G(2)-M CELL-CYCLE ARREST AND OR APOPTOSIS/

The retinoblastoma protein-interacting zinc finger gene RIZ maps to th e distal short arm of human chromosome I (1p36), a region thought to h arbor 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 prom oter and lacks an NH2-terminal motif of RIZ1, the PR domain conserved in a subfamily of zinc finger genes that function as negative regulato rs of tumorigenesis. We have here studied whether the RIZ gene may pla y a role in human neoplasia, We found that expression of RIZ1 is commo nly decreased or at undetectable levels in breast cancer tissues and c ell Lines. Decreased RIZ1 expression was also found in other tumor typ es including neuroblastoma and lung cancer. Remarkably, RIZ2 is normal ly expressed in all cases examined, suggesting that the abnormality ob served for RIZ1 is specific Forced RIZ1 expression in breast cancer ce lls caused cell cycle arrest in G(2)-M and/or programmed cell death, T hese observations suggest an exclusive negative selection for RIZ1 but not RIZ2 in breast cancer and a role for RIZI in tumor suppression.