HNF1 ACTIVATES TRANSCRIPTION OF THE HUMAN GENE FOR INSULIN-LIKE GROWTH-FACTOR BINDING PROTEIN-1

Insulin-like growth factor binding protein-1 (IGFBP-1) is expressed pr imarily in the liver, kidney, an uterus. Basal IGFBP-1 promoter activi ty in human HEP G2 hepatoma cells is dependent upon a proximal promote r element that binds hepatic nuclear factor 1 (HNF1), a protein that i s likely to be an important factor regulating the expression of many g enes in liver and kidney. To test whether HNF1 activates IGFBP-1 trans cription, HEP G2 cells and HeLa cells were cotransfected transiently w ith HNF1 expression vectors and with IGFBP-1 promoter/chloramphenicol acetyltransferase reporter gene constructs. HNF1 increased IGFBP-1 pro moter activity in both HEP G2 and HeLa cells. Gel mobility-shift assay s and additional transfections in HeLa cells showed that expressed ful l-length and carboxy-terminal truncated forms of HNF1 could each bind the HNF1 cis element of the IGFBP-1 promoter; however, significant tra ns-activation only occurred in the presence of the full-length HNF1 pr otein, similar to past experience with these two HNF1 forms and the al bumin promoter. Further studies showed that IGFBP-1 promoter construct s containing mutations with high or low affinity for HNF1 responded to HNF1 expression with increased or decreased activity, respectively, r elative to the native promoter. These studies suggest that HNF1 and/or related proteins play a role in hepatic, and perhaps also renal, expr ession of IGFBP-1.