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Alternatively spliced glucocorticoid receptor messenger RNAs in glucocorticoid-resistant human multiple myeloma cells

P A Moalli1, S Pillay, N L Krett

  • 1Department of Medicine, Northwestern University, Chicago, Illinois 60611.

Cancer Research
|September 1, 1993
PubMed

Insights

Glucocorticoids are vital for treating multiple myeloma but resistance is a challenge. This study reveals that alternative splicing of glucocorticoid receptors leads to resistance in myeloma cells.

Area of Science:

  • Molecular Biology
  • Oncology
  • Endocrinology

Background:

  • Glucocorticoids are effective chemotherapeutic agents for hematological malignancies like multiple myeloma.
  • Drug resistance significantly limits the clinical utility of glucocorticoids in cancer treatment.

Purpose of the Study:

  • To investigate the molecular mechanisms underlying glucocorticoid resistance in multiple myeloma.
  • To identify genetic alterations in the glucocorticoid receptor associated with drug resistance.

Main Methods:

  • Generation of a complementary DNA (cDNA) library from a glucocorticoid-resistant myeloma cell line (MM.1Re).
  • Isolation and characterization of alternatively spliced glucocorticoid receptor transcripts from the cDNA library.

Main Results:

  • Two alternatively spliced glucocorticoid receptor transcripts were identified.
  • Both transcripts featured precise deletions of specific exons within the hormone-binding domain.
  • These deletions suggest the generation of novel receptor isoforms.

Conclusions:

  • Alternative splicing is a key mechanism for generating glucocorticoid receptor isoforms.
  • These isoforms contribute to the development of glucocorticoid resistance in myeloma cells.
  • Understanding these mechanisms may offer new therapeutic strategies against drug-resistant cancers.

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