Analysis of glucocorticoid-inducible genes in wild-type and variant rat hepatoma cells

We present pharmacological and genetic evidence that regulation of different genes by glucocorticoid hormones in the rat hepatoma cell line, HTC, occurs in a coordinate manner. We have analyzed the responses of four different glucocorticoid-inducible proteins, tyrosine aminotransferase [L-tyrosine:2-oxoglutarate aminotransferase (EC 2.6.1.5)], glutamine synthetase [L-glutamate:ammonia ligase (EC 6.3.1.2)], a secreted glycoprotein Belt I, and the mouse mammary tumor virus (MMTV)-encoded protein (gp52) in these cells. The concentration of dexamethasone necessary for half-maximal induction of each of these proteins is 10-20 nM, the same concentration necessary to half-saturate glucocorticoid receptors. Furthermore, glucocorticoids of varying potency elicit parallel inductions of these markers. MSN5.3, a glucocorticoid receptor-defective cell line selected for its inability to induce gp52, is also unable to induce the other three cellular gene products. In contrast, another class of variants incapable of gp52 induction retains inducibility of the other three markers. We show here by "superinfection" with MMTV that these cells harbor a defect in the original integrated provirus itself and not in the cellular induction machinery. The results presented here suggest that the induction of glucocorticoid-responsive genes in these cells is mediated by a single glucocorticoid induction pathway.