Journal
MOLECULAR AND CELLULAR ENDOCRINOLOGY
Volume 361, Issue 1-2, Pages 124-132Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.mce.2012.03.024
Keywords
c-Myb; Glucocorticoid receptor; Acute lymphoblastic leukemia; Auto-upregulation
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Funding
- NCI Grant [CA116042]
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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. (c) 2012 Elsevier Ireland Ltd. All rights reserved.
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