TY - JOUR
T1 - The direct Myc target Pim3 cooperates with other Pim kinases in supporting viability of Myc-induced B-cell lymphomas
AU - Forshell, Linus Plym
AU - Li, Yongmei
AU - Forshell, Tacha Zi Plym
AU - Rudelius, Martina
AU - Nilsson, Lisa
AU - Keller, Ulrich
AU - Nilsson, Jonas
PY - 2011/6
Y1 - 2011/6
N2 - The Pim kinases are weak oncogenes. However, when co-expressed with a strong oncogene, such as c-Myc, Pim kinases potentiate the oncogenic effect resulting in an acceleration of tumorigenesis. In this study we show that the least studied Pim kinase, Pim-3, is encoded by a gene directly regulated by c-Myc via binding to one of the conserved E-boxes within the Pim3 gene. Accordingly, lymphomas arising in Myc-transgenic mice and Burkitt lymphoma cell lines exhibit elevated levels of Pim-3. Interestingly, inhibition of Pim kinases by a novel pan-Pim kinase inhibitor, Pimi, in Myc-induced lymphoma results in cell death that appears independent of caspases. The data indicate that Pim kinase inhibition could be a viable treatment strategy in certain human lymphomas that rely on Pim-3 kinase expression.
AB - The Pim kinases are weak oncogenes. However, when co-expressed with a strong oncogene, such as c-Myc, Pim kinases potentiate the oncogenic effect resulting in an acceleration of tumorigenesis. In this study we show that the least studied Pim kinase, Pim-3, is encoded by a gene directly regulated by c-Myc via binding to one of the conserved E-boxes within the Pim3 gene. Accordingly, lymphomas arising in Myc-transgenic mice and Burkitt lymphoma cell lines exhibit elevated levels of Pim-3. Interestingly, inhibition of Pim kinases by a novel pan-Pim kinase inhibitor, Pimi, in Myc-induced lymphoma results in cell death that appears independent of caspases. The data indicate that Pim kinase inhibition could be a viable treatment strategy in certain human lymphomas that rely on Pim-3 kinase expression.
KW - Animals
KW - Caspase 3/metabolism
KW - Cell Line, Tumor
KW - Cell Survival/drug effects
KW - Cell Transformation, Neoplastic/drug effects
KW - Gene Expression Regulation, Neoplastic/drug effects
KW - Humans
KW - Lymphoma, B-Cell/genetics
KW - Mice
KW - Mice, Transgenic
KW - NIH 3T3 Cells
KW - Protein Kinase Inhibitors/pharmacology
KW - Protein Serine-Threonine Kinases/antagonists & inhibitors
KW - Proto-Oncogene Proteins/antagonists & inhibitors
KW - Proto-Oncogene Proteins c-myc/genetics
KW - Proto-Oncogene Proteins c-pim-1/antagonists & inhibitors
U2 - 10.18632/oncotarget.283
DO - 10.18632/oncotarget.283
M3 - Article
C2 - 21646687
SN - 1949-2553
VL - 2
SP - 448
EP - 460
JO - Oncotarget
JF - Oncotarget
IS - 6
ER -