Selective loss of glucocorticoid-dependent responses in a variant of the DDT1MF-2 tumor cell line.
Glucocorticoid treatment dramatically inhibits growth of the wild-type DDT1MF-2 hamster smooth muscle tumor cell line (DDT-WT) but not that of a glucocorticoid-selected clonal variant (DDT-GR). Our objective was to further define the level of glucocorticoid resistance in DDT-GR cells. Glucocorticoid receptors were confirmed to be less abundant in DDT-GR cells, but the immunoreactivity and molecular dimensions of the receptor and the ability of the receptor to undergo ligand-dependent nuclear accumulation was the same as that in DDT-WT cells. Glucocorticoid treatment also stimulated expression of the beta 2-adrenergic receptor gene to the same extent (approximately 2-fold at the mRNA and membrane protein level) in both cell lines. With the exception of the previously identified p29 protein, the pattern of detectably altered protein synthesis during glucocorticoid treatment was identical in both cell lines. All of the above responses that were shared by DDT-WT and DDT-GR cells as well as growth inhibition and p29 induction which are restricted to the DDT-WT cell could be blocked by the antiglucocorticoid, 17 beta-hydroxy-11 beta-[4-(dimethylamino)phenyl]-17 alpha-propynylestra- 4,9-dien-3-one. Together, these data indicate that DDT-GR cells contain enough functional glucocorticoid receptors to successfully regulate most of the normally responsive genes. Exploitation of this fact should greatly facilitate efforts to identify and study the function of those genes that are specifically involved in the antiproliferative action of glucocorticoid on the DDT-WT cell.
Hendry
W J
WJ
Department of Medicine, University of Arkansas for Medical Sciences, Little Rock 72205.
Hakkak
R
R
Cornett
L E
LE
D000818:Animals; D000936:Antigen-Antibody Complex / Q000302:isolation & purification; D006224:Cricetinae; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D005938:Glucocorticoids / Q000494:pharmacology; D007890:Leiomyosarcoma / Q000737:chemistry* / Q000378:metabolism; D009363:Neoplasm Proteins / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D011942:Receptors, Adrenergic, alpha / Q000235:genetics; D011965:Receptors, Glucocorticoid / Q000032:analysis* / Q000378:metabolism; D014407:Tumor Cells, Cultured
D000936:Antigen-Antibody Complex; D005938:Glucocorticoids; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D011942:Receptors, Adrenergic, alpha; D011965:Receptors, Glucocorticoid