Isolation of new types of dexamethasone-resistant variants from a cAMP-resistant lymphoma
Abstract
We have developed a sequential selection procedure for the isolation of novel steroid-resistant variants of the murine thymoma WEHI-7. The first step involves the isolation of cell lines with an altered cAMP-dependent protein kinase (cAPK) activity by selection for resistance to dibutyryl cAMP (dbcAMP). The second step involves the selection for resistance to dexamethasone (dex) which results in the isolation of variants with decreased receptor function and a cAMPrdexr phenotype. The initial selection, to cAMPr, serves as a permissive step since isolation of spontaneous glucocorticoid resistance from wild-type WEHI-7 does not occur at a measurable frequency. The results demonstrate a potential role for cAPK in regulating the functional levels of glucocorticoid receptor and suggest that mutations in other cellular functions that affect receptor activity could lead to steroid resistance in lymphoid cells.
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cAMP-resistant cell lines give rise to a significantly higher frequency of glucocorticoid-resistant cell variants.
“cAMP-resistant cell lines have been shown to give rise to a significantly higher frequency of glucocorticoid-resistant cell variants.113”
From Cytokines and Glucocorticoid Receptor Signaling (2009) · cites this paper as [113]
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Cytokines and Glucocorticoid Receptor Signaling
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- Authors
- Gruol, D. J., Ashby, M. N., Campbell, N. F., & Bourgeois, S.
- Affiliations
- Salk Institute for Biological Studies (US)
- Venue
- Journal of Steroid Biochemistry
- Publisher
- Elsevier BV
- Published
- 1986-01
- Volume
- 24
- Issue
- 1
- Pages
- 255-258
- ISSN
- 0022-4731 (ISSN-L)
- OpenAlex
- W2038731320
- Cited by
- 7
- References
- 19
- FWCI
- 0.49
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Steroid Biochemistry (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Cancer Institute (CA 36146)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Receptor Mechanisms and Signaling
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
- Keywords
- dexamethasone resistance, glucocorticoid resistance, protein kinase A, glucocorticoid receptor, sequential selection, lymphoid cells
- MeSH terms
- Cyclic AMP, Animals, Cell Line, Dexamethasone, Bucladesine, Drug Resistance, Lymphoma, Mice, Inbred BALB C, Mutation, Phenotype, Protein Kinases, Receptors, Glucocorticoid, Mice
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