Regulation of metallothionein II messenger ribonucleic acid measures exogenous estrogen receptor-beta activity in SAOS-2 and LNCaPLN3 cells.

Estrogen receptor-beta (ERbeta) is a recently discovered member of the steroid hormone superfamily. Because its distribution is distinct from that of the classical estrogen receptor, and it is expressed in several nonclassical estrogen target tissues (e.g. prostate and bladder), its role in mediating the action of estrogen is unclear. One approach to elucidating the function of this receptor is to identify genes that it regulates. Using differential display, we profiled the messenger RNAs regulated by 17beta-estradiol in SAOS-2 and LNCaPLN3 cells overexpressing ERbeta. Follow-up studies used cells expressing either ERalpha or ERbeta. One gene, metallothionein II, was regulated by both receptor subtypes in LNCaPLN3 cells, but only by ERbeta in SAOS-2 cells. Because cycloheximide blocks this response, induction is probably mediated through regulation of at least one other protein. Identification of endogenous genes that are regulated differentially by ERalpha and ERbeta will be valuable tools in elucidating the function of ERbeta and the mechanisms by which these two receptors regulate transcription.