Specific receptors control steroid sensitivity in lymphoma cell hybrids

Area of Science:

• Cell Biology
• Genetics
• Molecular Endocrinology

Background:

• Mouse lymphoma cell lines, including S49.1 variants (wild-type, receptor binding-defective, nuclear transfer-defective) and EL4 (nuclear transfer-defective), were utilized.
• Understanding glucocorticoid receptor (GR) function and gene localization is crucial in endocrinology and cancer research.

Purpose of the Study:

• To investigate the genetic basis of glucocorticoid resistance in mouse lymphoma cells.
• To develop a cell system for mapping the glucocorticoid receptor gene to a specific mouse chromosome.

Main Methods:

• Hybridization of different S49.1 sub-lines with EL4 lymphoma cells.
• Phenotypic analysis of hybrid cells for glucocorticoid sensitivity, receptor binding, and nuclear transfer.
• Selection of resistant segregants from sensitive hybrid clones and chromosomal analysis.

Main Results:

• Wild-type glucocorticoid sensitivity was dominant over nuclear transfer-defective resistance.
• The receptor binding-defective and nuclear transfer-defective phenotypes did not complement, suggesting a defect in the same polypeptide.
• Resistant segregants frequently lost a chromosome, correlating with the loss of wild-type S49.1 receptor, indicating hemizygosity of the GR gene.

Conclusions:

• The study provides direct evidence for the hemizygosity of the glucocorticoid receptor gene in S49.1 cells.
• The developed cell system is suitable for assigning the glucocorticoid receptor gene to a specific mouse chromosome.