Converting cell lines representing hematological malignancies from glucocorticoid-resistant to glucocorticoid-sensitive: signaling pathway interactions.
Mitogen-activated protein kinases (MAPKs), protein kinase A (PKA) and mTOR pathways modulate the apoptotic effects of glucocorticoids (GCs) in human lymphoblastic leukemia CEM cells. We now show that manipulation of these pathways converts several cell lines, representing other lymphoid malignancies, from GC-resistant to GC-sensitive. Basal levels of phosphorylated JNK and ERK were elevated in the GC-resistant cells. Treatments that directly or indirectly reduced phosphorylated JNK and ERK resulted in Dex sensitivity in five resistant lymphoid cell lines. Sensitivity to GC-driven apoptosis correlated with GC-dependent increases in phosphorylated and total glucocorticoid receptor, and in increased levels of the pro-apoptotic protein Bim.
Garza
Anna S
AS
The University of Texas Medical Branch, Department of Biochemistry and Molecular Biology, Galveston, TX 77555-1068, USA.
Miller
Aaron L
AL
Johnson
Betty H
BH
Thompson
E Brad
EB
D017209:Apoptosis; D045744:Cell Line, Tumor; D003907:Dexamethasone / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm; D019337:Hematologic Neoplasms / Q000201:enzymology / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D010766:Phosphorylation; D015398:Signal Transduction
D003907:Dexamethasone; D020928:Mitogen-Activated Protein Kinases