Specific receptors control steroid sensitivity in lymphoma cell hybrids.
Hybrids between different mouse lymphoma cell lines were prepared. 3 sub-lines of S49.1 were used: one of them was glucocorticoid-sensitive (wild-type, wt), the others were resistant with defects either in receptor binding (r-) or in nuclear transfer of the receptor-glucocorticoid complex (nt-). These cells were hybridized with another glucocorticoid-resistant lymphoma, EL4, which is of the nt- phenotype. wild-type glucocorticoid sensitivity was dominant over nt- resistance, and S49.1 wt X EL4 hybrids contained glucocorticoid receptors of both parental cell types. The r- and nt- phenotypes did not complement, suggesting that both defects occurred in the same polypeptide. S49.1 wt X EL4 hybrids produced resistant cells at 3 XC 10(-4) per cell per generation. Sensitive hybrid cell clones were treated with high glucocorticoid doses to select for resistant segregants. The majority of these segregants had lost one chromosome. The concomitant loss of the wild-type S49.1 receptor was observed upon transition from sensitivity to resistance. These results provide direct evidence for the hemizygosity of the glucocorticoid receptor gene in S49.1 cells. Thus, the cell system described here is suitable for assigning the glucocorticoid receptor gene to a specific mouse chromosome.
D000818:Animals; D002460:Cell Line; D003907:Dexamethasone / Q000378:metabolism / Q000494:pharmacology; D004351:Drug Resistance; D006822:Hybrid Cells / Q000378:metabolism; D008223:Lymphoma / Q000378:metabolism*; D051379:Mice; D011965:Receptors, Glucocorticoid / Q000378:metabolism*; D011987:Receptors, Steroid / Q000378:metabolism*
D011965:Receptors, Glucocorticoid; D011987:Receptors, Steroid; D003907:Dexamethasone