HZAC ENCODES A ZINC-FINGER PROTEIN WITH ANTIPROLIFERATIVE PROPERTIES AND MAPS TO A CHROMOSOMAL REGION FREQUENTLY LOST IN CANCER

We previously reported the identification of mZac, a novel mouse zinc finger protein that shared with p53 the ability to regulate concomitan tly apoptosis and cell cycle progression. We describe here the isolati on, chromosomal localization, and functional in vitro characterization of its human homolog. hZAC is a widely expressed zinc finger protein that reveals transactivation and DNA-binding activity. hZAC inhibits t umor cell growth through induction of apoptotic cell death and G(1) ar rest. Thus hZAC, like its mouse counterpart, displays antiproliferativ e properties through pathways known to be central to the activity of p 53, We mapped hZAC on chromosome 6q24-q25, a region frequently deleted in many solid tumors. Indeed, allelic loss at 6q24-q25 has been shown in breast and ovary cancers, melanomas, astrocytomas, and renal cell carcinomas. Furthermore, Abdollahi et al. [Abdollahi, A., Godwin, A. K ., Miller, P. D., Getts, L. A., Schultz, D. C., Tagushi, T., Testa, J. R. & Hamilton, T.C. (1997) Cancer Res. 57, 2029-2034] recently isolat ed ZAC through its loss of expression in a surface epithelial ovary tu mor model and accordingly named it Lot for ''lost on transformation,'' In view of these observations, the functional properties we report he re provide further arguments to consider hZAC as a tumor suppressor ge ne candidate.