Related Experiment Videos
Deletion of a consensus oestrogen response element half-site in the glucocorticoid receptor of human multiple myeloma
J D Karkera1, S E Taymans, G Turner
1Medical Oncology Section, Department of Veterans Affairs Medical Center, Washington, D.C. 20422, U.S.A.
Abstract:
We have carried out molecular scanning of the glucocorticoid receptor (GR) of the glucocorticoid resistant multiple myeloma cell line U266. An amplified fragment from the 3' untranslated region displayed an aberrant migration by PCR-single-stranded conformational polymorphism (PCR-SSCP) analysis. The mutant allele had a deletion of an 8 base pair sequence containing a half-site of an oestrogen response element. This motif was found conserved in rat GR. This same allele lacked four As in an upstream region with 18 consecutive As in the normal allele. These mutations may affect mRNA stability or alter interactions with regulatory factors.
Insights
Glucocorticoid receptor (GR) mutations in multiple myeloma cells were identified. A deletion in the 3' untranslated region may impact mRNA stability and gene regulation.
Area of Science:
- Molecular biology
- Genetics
- Cancer research
Background:
- Multiple myeloma is a cancer of plasma cells.
- Glucocorticoid resistance is a challenge in multiple myeloma treatment.
- The glucocorticoid receptor (GR) plays a role in cellular response to glucocorticoids.
Purpose of the Study:
- To investigate the molecular basis of glucocorticoid resistance in the U266 multiple myeloma cell line.
- To identify mutations in the glucocorticoid receptor (GR) gene.
Main Methods:
- Molecular scanning of the glucocorticoid receptor (GR) in U266 cells.
- Polymerase chain reaction-single-stranded conformational polymorphism (PCR-SSCP) analysis.
- DNA sequencing to identify mutations.
Main Results:
- An aberrant migration pattern was observed in a PCR-amplified fragment from the 3' untranslated region of the GR gene.
- A mutant allele exhibited an 8 base pair deletion within a half-site of an oestrogen response element (ERE).
- The mutant allele also showed a difference in a polyadenine tract compared to the normal allele.
Conclusions:
- The identified mutations in the GR 3' untranslated region may contribute to glucocorticoid resistance.
- These genetic alterations could affect messenger RNA (mRNA) stability.
- The mutations might influence interactions with other regulatory factors, impacting gene expression.