title: c-Myb interacts with the glucocorticoid receptor and regulates its level in pre-B-acute lymphoblastic leukemia cells.
abstract: Glucocorticoid (GC) hormones are used in the treatment of hematopoietic malignancies. When the GC binds to the glucocorticoid receptor (GR) protein, c-Myb and GR are recruited at the Glucocorticoid Response Unit in the DNA. Here we demonstrate that c-Myb interacts with the GR and that decreasing c-Myb amounts reduces the levels of GR transcripts and protein in 697 pre-B-acute lymphoblastic leukemia (ALL) cells. Furthermore, the auto-upregulation of GR promoter 1C and promoter 1D is blunted at reduced c-Myb levels. Taken together, these data show that c-Myb is a direct, key regulator of the GR. Unexpectedly, the reduction in c-Myb levels increased the sensitivity of the cells to steroid-mediated apoptosis. This was because the reduction in c-Myb itself decreases cell viability, and the residual GR remained above the threshold needed to trigger apoptosis. These studies show the mutual importance of c-Myb and the GR in controlling survival of pre-B ALL cells.
authors.affiliation: Department of Biochemistry and Molecular Biology, Stanley S. Scott Cancer Center, Louisiana State University Health Sciences Center, New Orleans, LA 70112, United States.
authors.forename: Purvaba J
authors.initials: PJ
authors.lastname: Sarvaiya
authors.forename: Jason R
authors.initials: JR
authors.lastname: Schwartz
authors.forename: Chuan-dong
authors.initials: CD
authors.lastname: Geng
authors.forename: Wayne V
authors.initials: WV
authors.lastname: Vedeckis
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D003907:Dexamethasone / Q000494:pharmacology; D004318:Doxycycline / Q000494:pharmacology; D015973:Gene Expression Regulation, Leukemic / Q000187:drug effects; D055785:Gene Knockdown Techniques; D006801:Humans; D051379:Mice; D015452:Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding / Q000187:drug effects; D020598:Proto-Oncogene Proteins c-myb / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011965:Receptors, Glucocorticoid / Q000235:genetics / Q000378:metabolism*; D013256:Steroids / Q000494:pharmacology; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics
chemical_list: D020598:Proto-Oncogene Proteins c-myb; D012333:RNA, Messenger; D011965:Receptors, Glucocorticoid; D013256:Steroids; D003907:Dexamethasone; D004318:Doxycycline