Alternatively spliced glucocorticoid receptor messenger RNAs in glucocorticoid-resistant human multiple myeloma cells.
Glucocorticoids are highly effective chemotherapeutic agents used in the treatment of hematological malignancies including multiple myeloma. However, the clinical usefulness of this class of drugs is limited by the problem of resistance. In the following study, we have isolated two alternatively spliced transcripts of the glucocorticoid receptor from a complementary DNA library generated from the glucocorticoid-resistant myeloma cell line MM.1Re. In each of the clones, specific exons of the hormone binding domain are precisely deleted. Our data implicate alternate splicing as a mechanism by which a cell generates different receptor isoforms and as a consequence evades the effects of hormone.
Moalli
P A
PA
Department of Medicine, Northwestern University, Chicago, Illinois 60611.
Pillay
S
S
Krett
N L
NL
Rosen
S T
ST
D017398:Alternative Splicing; D001483:Base Sequence; D004351:Drug Resistance / Q000235:genetics; D005091:Exons; D017353:Gene Deletion; D006801:Humans; D008969:Molecular Sequence Data; D009101:Multiple Myeloma; D012333:RNA, Messenger / Q000235:genetics / Q000302:isolation & purification*; D011965:Receptors, Glucocorticoid / Q000737:chemistry* / Q000235:genetics; D014407:Tumor Cells, Cultured
D012333:RNA, Messenger; D011965:Receptors, Glucocorticoid