This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Hendry, W. J. Articles by Cornett, L. E. Search for Related Content PubMed PubMed Citation Articles by Hendry, W. J., III Articles by Cornett, L. E.

Selective Loss of Glucocorticoid-dependent Responses in a Variant of the DDT₁MF-2 Tumor Cell Line¹

Department of Medicine, Division of Endocrinology/Metabolism [W. J. H., R. H.], Department of Biochemistry and Molecular Biology [W. J. H.], and Department of Physiology and Biophysics [L. E. C.], University of Arkansas for Medical Sciences, Little Rock, Arkansas 72205

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 ß₂-adrenergic receptor gene to the same extent (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, 17ß-hydroxy-11ß-[4-(dimethylamino)phenyl]-17-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.

¹ This work was supported by United States Health Service Grants DK 38025, CA 42091 (W.J.H.), and GM 30669 (L.E.C.).

² To whom requests for reprints should be addressed, at the Department of Biological Sciences, 1845 North Fairmount, Hubbard Hall, Box 26, Wichita State University, Wichita, KS 67208.

Received 10/31/91. Accepted 2/26/92.