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High incidence and characterization of glucocorticoid receptors in human malignant melanoma
Abstract:
The glucocorticoid receptor was characterized in biopsy samples from patients with recurrent malignant melanoma. Glucocorticoid receptors were measured by the charcoal-adsorption technique. Tumor cytosol from approximately 86% (25/29) of the patients contained large quantities of receptors (20-324 fmol/mg protein). The dissociation constant of this cytoplasmic receptor was determined to be 2-22 nM. This binding component sedimented at 7.1S on sucrose gradients of low ionic strength and dissociated into lower molecular weight components that sedimented at 4.4S on sucrose gradients of high ionic strength. Receptor binding was specific for glucocorticoids. Although progestins competed well for the binding that is typical for glycocorticoid receptor as reported in the literature, other steroids, e.g., 17 beta-estradiol and 5 alpha-dihydrotestosterone, were only weak competitors. These results demonstrated that this neoplasm contains large quantities of glucocorticoid receptors that are similar in their physicochemical characteristics to those found in normal tissues. This finding in human melanoma biopsy specimens may be of therapeutic value in the management of patients with malignant melanoma.
Insights
Malignant melanoma tumors frequently contain abundant glucocorticoid receptors, similar to those in normal tissues. This discovery suggests potential therapeutic strategies for managing melanoma patients.
Area of Science:
- Oncology
- Endocrinology
- Molecular Biology
Background:
- Malignant melanoma is a significant health concern.
- Understanding cellular receptors in cancer is crucial for targeted therapies.
Purpose of the Study:
- To characterize glucocorticoid receptors in malignant melanoma biopsy samples.
- To assess the potential therapeutic implications of these receptors.
Main Methods:
- Utilized the charcoal-adsorption technique to quantify glucocorticoid receptors.
- Employed sucrose gradient centrifugation to determine receptor characteristics.
- Performed steroid competition assays to confirm binding specificity.
Main Results:
- Glucocorticoid receptors were detected in 86% of melanoma samples, with high quantities (20-324 fmol/mg protein).
- Receptor dissociation constant was determined to be 2-22 nM.
- Physicochemical properties of melanoma glucocorticoid receptors resemble those in normal tissues, with specific binding to glucocorticoids.
Conclusions:
- Human melanoma exhibits substantial levels of glucocorticoid receptors.
- The identified receptors share characteristics with those in normal tissues.
- The presence of these receptors may offer a therapeutic target for malignant melanoma management.