EXPRESSION OF MT-3 MESSENGER-RNA IN HUMAN KIDNEY, PROXIMAL TUBULE CELL-CULTURES, AND RENAL-CELL CARCINOMA

The human metallothionein 3 (MT-3) gene has recently been identified a nd characterized as a brain-specific MT having growth inhibitory activ ity for neuronal cells. One objective of the present study was to dete rmine if MT-3 is brain-specific or also present in the renal system, a site for chronic toxicity due to heavy metal exposure. Using RT-PCR m ethodology, MT-3 mRNA was shown to be expressed in the human renal sys tem at levels below mRNA for the beta-actin gene. MT-3 mRNA was shown to be expressed in all samples obtained from both the developing and a dult renal systems, from 20 weeks of fetal age to 72 years. Cultures o f human proximal tubule (HPT) cells were used to determine if MT-3 mRN A expression is influenced by metal exposure. Exposure of HPT cells to either Zn2+ or Cd2+ resulted in an early (within 24 h), but unsustain ed increase in MT-3 mRNA. The demonstration of MT-3 mRNA expression in the kidney indicates that MT-3 may play an important early role in th e response of the cell to metal exposure. MT-3 mRNA expression was als o examined in tissues and cells from three cases of renal cell carcino ma. MT-3 was found to be expressed in all three cases at levels simila r to those found for normal kidney, providing evidence that MT-3 mRNA expression is not altered in this cancer. (C) 1997 Elsevier Science Ir eland Ltd.