The effects of a v-mos oncoprotein on glucocorticoid-induction of metallothionein-1 (Mt-1) gene expression have been evaluated using the rat 6m2 cell line, in which expression of the p85gag- mos oncogene, and consequently transformation, are temperature- sensitive (ts). The p85gag-mos oncogene, and consequently transformation, are temperature-sensitive (ts). The temperature-dependent expression of p85gag-mos in 6m2 cells resulted in only a transient dexamethasone induction of Mt-1 levels, that rapidly declined to uninduced levels despite the continued presence of hormone. Nuclear run-on assays will be performed to determine to what extent transient induction of Mt-1 mRNA levels reflect v-mos effects on transcription. The examination of the kinetics and reversibility of desensitized Mt- 1 expression, using both temperature-shift experiments and hormone withdrawal and restimulation, will reveal whether v-mos accelerates a "normal" deinduction process or affects an independent desensitization pathway. Glucocorticoid regulated expression, both positive and negative of endogenous and transfected genes will be analyzed in various ts v-mos- transformed cell types. These analyses will determine whether oncoprotein effects can be distinguished for hormonal responses that may be cell type specific and subject to multi-hormonal control. They will also allow corrorlations, if any exist, between v-mos mediated alterations in hormone regulated gene expression and glucocorticoid receptor function.
