Glucocorticoid regulation of the mouse metallothionein I gene is selectively lost following amplification of the gene.

The mouse metallothionein I (MT-I) gene is regulated by both heavy metals and glucocorticoid hormones. We selected cadmium-resistant variants of the mouse sarcoma cell line, S180, in which the metallothionein I gene has been amplified 10-fold and found that the amplified genes are regulated by cadmium in a manner identical with that observed for the original MT-I gene in unselected S180 cells. However, the amplified metallothionein I genes appear to be essentially nonresponsive to glucocorticoids even though at least 18 kilobases of DNA flanking the 5' side of the metallothionein I gene are amplified in these cells. The same result has been observed in nine clonal lines derived from the cadmium-resistant (CdR) population. The implications of this result both for models of steroid hormone action and for gene evolution are discussed.