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.
D000818:Animals; D002104:Cadmium / Q000494:pharmacology; D002460:Cell Line; D003001:Cloning, Molecular; D003907:Dexamethasone / Q000494:pharmacology*; D005784:Gene Amplification / Q000187:drug effects*; D005796:Genes / Q000187:drug effects*; D014644:Genetic Variation; D007700:Kinetics; D008667:Metalloproteins / Q000235:genetics*; D008668:Metallothionein / Q000235:genetics*; D051379:Mice; D012333:RNA, Messenger / Q000235:genetics; D012513:Sarcoma, Experimental / Q000378:metabolism*; D014158:Transcription, Genetic
D008667:Metalloproteins; D012333:RNA, Messenger; D002104:Cadmium; D003907:Dexamethasone; D008668:Metallothionein