Transcription of metallothionein isoform promoters is differentially regulated in cadmium-sensitive and -resistant CHO cells.

Transcription regulation of metallothionein (MT) isoform promoters was investigated in Chinese hamster ovary (CHO) K1 and MT gene amplified, cadmium-resistant (CdR) cells. The transfected promoter of Chinese hamster MTI and MTII genes can be activated in both cell lines by stimulation with Cd or Zn ions, although no MT mRNA can be detected in CHO K1 cells after challenge with metal ions. Neither MT promoter used in this study can be activated by induction with dexamethasone, regardless of whether a sequence homologous to glucocorticoid responsive element is present. During induction by metal ions, differential promoter activities of the MT genes occurs in both CHO K1 and CdR cells where MTII promoter has a stronger activity than that of MTI. As indicated by a time course study in both cell lines, the relative induction ratios of both MTI and MTII promoters are similar at each time interval. This result is consistent with a differential transcriptional factor-promoter interaction for the two MT promoters. By using the CHO K1 and CdR cells as a model system, the occurrence of autoregulation for yeast CUP1 (MT) gene was examined in mammalian cells. Both MT promoters consistently show a lower basal activity but a higher induction ratio in CHO K1 than CdR cells; a result different from that of yeast CUP1 gene. When MTF-1 mRNA was examined, no difference in relative quantity was observed in CHO K1 and in CdR cells treated with metal ions or with metal ions absent.