p38-MAP kinase activation followed by BIM induction is essential for glucocorticoid-induced apoptosis in lymphoblastic leukemia cells.
Glucocorticoids (GC) are common components in chemotherapeutic protocols for lymphoid malignancies. GC-induced apoptosis requires the intrinsic, BCL-2 family-regulated pathway. Treatment of CCRF-CEM (T cell acute lymphoblastic leukemia) cells with the GC, dexamethasone (Dex), activates p38-mitogen activated protein kinase (p38-MAPK) and then induces mRNA transcription and synthesis levels of BIM, a BH3-only pro-apoptotic BCL-2 family member. Dex-induced apoptosis is dramatically inhibited by downregulation of BIM by shRNA or by pretreatment with a p38-MAPK inhibitor, SB203580, which also reduces BIM induction. These findings indicate that BIM induction through p38-MAPK activation is a critical pathway in GC-induced cell death.
Lu
Jianghua
J
Department of Internal Medicine, Massey Cancer Center, Virginia Commonwealth University, Medical Sciences Building 215, Richmond, 23298, USA.
Quearry
Bonnie
B
Harada
Hisashi
H
D017209:Apoptosis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins / Q000096:biosynthesis*; D001483:Base Sequence; D000072224:Bcl-2-Like Protein 11; D015153:Blotting, Western; D045744:Cell Line, Tumor; D017931:DNA Primers; D003907:Dexamethasone / Q000494:pharmacology*; D004789:Enzyme Activation; D006801:Humans; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000201:enzymology / Q000473:pathology*; D008565:Membrane Proteins / Q000096:biosynthesis*; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
D051017:Apoptosis Regulatory Proteins; C000606775:BCL2L11 protein, human; D000072224:Bcl-2-Like Protein 11; D017931:DNA Primers; D008565:Membrane Proteins; D011518:Proto-Oncogene Proteins; D003907:Dexamethasone; D048051:p38 Mitogen-Activated Protein Kinases