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Down-regulation of glucocorticoid receptors in mouse lymphoma cell variants
Abstract:
The mouse thymoma-derived cell line W7 is sensitive to the cytolytic action of glucocorticoids. We have isolated a novel class of cell variant that apparently overcomes its inherent sensitivity to glucocorticoids by reversibly down-regulating the level of glucocorticoid receptors. This phenotype is stable during subcloning in the presence and in the absence of glucocorticoids and is dominant in somatic cell hybrids with wild-type cells. Fusion of this variant with wild-type cells produces hybrids that down-regulate and are less sensitive to glucocorticoids than hybrids of receptor-negative and wild-type cells. This is the first demonstration of a phenotypic change which correlates with down-regulation of the glucocorticoid receptor.
Insights
Researchers identified a new cell variant that reduces glucocorticoid receptor levels, making it less sensitive to these hormones. This finding demonstrates a link between receptor down-regulation and altered cell sensitivity.
Area of Science:
- Cell biology
- Molecular endocrinology
- Cancer research
Background:
- The W7 mouse thymoma cell line exhibits sensitivity to glucocorticoids.
- Glucocorticoids are potent regulators of cellular processes, including apoptosis.
Purpose of the Study:
- To investigate the mechanisms underlying glucocorticoid resistance in W7 cells.
- To isolate and characterize novel cell variants with altered glucocorticoid sensitivity.
Main Methods:
- Isolation and characterization of glucocorticoid-resistant cell variants.
- Phenotypic analysis of cell variants and somatic cell hybrids.
- Assessment of glucocorticoid receptor levels and cellular responses.
Main Results:
- A novel cell variant was isolated that reversibly down-regulates glucocorticoid receptor levels.
- This down-regulation confers resistance to glucocorticoid-induced cytotoxicity.
- The resistant phenotype is dominant in somatic cell hybrids with wild-type cells.
Conclusions:
- Down-regulation of glucocorticoid receptors is a mechanism for acquiring resistance to glucocorticoids.
- This study provides the first evidence linking a phenotypic change to glucocorticoid receptor down-regulation.