Related Experiment Videos
Glucocorticoid-resistant human acute lymphoblastic leukemic cell line with functional receptor
Cancer Research
|August 1, 1983
Summary
CEM-C1 cells, resistant to glucocorticoids, possess normal functional receptors. This suggests resistance stems from defects beyond the receptor itself, impacting cellular response to steroid treatments.
Area of Science:
- Cell Biology
- Molecular Pharmacology
- Endocrinology
Background:
- Glucocorticoids are crucial regulators of cellular processes, and resistance can impair therapeutic efficacy.
- Understanding the mechanisms of steroid resistance is vital for developing effective treatments.
Purpose of the Study:
- To investigate the characteristics of glucocorticoid receptors in a steroid-resistant cell line (CEM-C1).
- To compare these receptors with those in a steroid-sensitive cell line (CEM-C7).
- To identify the locus of glucocorticoid resistance in CEM-C1 cells.
Main Methods:
- Whole-cell binding assays using [3H]dexamethasone.
- Ion-exchange chromatography (DEAE cellulose) and gel filtration (Sephacryl S-300).
- DNA-cellulose binding assays and measurement of dexamethasone-induced glutamine synthetase activity.
Main Results:
- CEM-C1 cells displayed normal glucocorticoid receptor binding affinity (Kd), nuclear translocation (nt), and receptor number (R0), similar to CEM-C7 cells.
- Physicochemical properties, including ion-exchange and gel filtration profiles, were indistinguishable between CEM-C1 and CEM-C7 receptors.
- Dexamethasone effectively induced glutamine synthetase in CEM-C1 cells, comparable to CEM-C7 cells, indicating functional downstream signaling.
Conclusions:
- CEM-C1 cells possess apparently normal, functional cytosolic glucocorticoid receptors.
- Steroid resistance in CEM-C1 cells likely involves defects at a post-receptor locus.
- Further research is needed to pinpoint the specific molecular defect causing glucocorticoid resistance.