ZBP-89, A KRUPPEL-TYPE ZINC-FINGER PROTEIN, INHIBITS CELL-PROLIFERATION

ZBP-89 is a Kruppel-type zinc finger transcription factor that binds t o GC-rich sequences. Overexpression of this factor prevents EGF induct ion of the gastrin promoter; therefore, we postulated that ZBP-89 may modulate cellular proliferation. To test this hypothesis, ZBP-89 was o verexpressed in immortalized (GH(4)) and malignant (AGS) cell lines. G rowth parameters, e.g., H-3-thymidine, BrdU labeling, flow cytometry a nd ornithine decarboxylase promoter activity were analyzed. The result s show that DNA synthesis is inhibited and progression to S phase is b locked in GH(4) cells. Collectively, these studies demonstrate that ZB P-89 inhibits cellular proliferation at least in part through its abil ity to bind and repress ornithine deacarboxlyase promoter activity. (C ) 1997 Academic Press.