ArticleJournal of cancer research and clinical oncology2008
Additive effects of PI3-kinase and MAPK activities on NB4 cell granulocyte differentiation: potential role of phosphatidylinositol 3-kinase gamma.
Article in Journal of cancer research and clinical oncology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed, 12 citations in OpenAlex.
- Multi-omics profiling identifies C1QA/BAnnals of translational medicine · 2022Article
- Biological Aspects of mTOR in Leukemia.International journal of molecular sciences · 2018Review
- Targeting PI3K/AKT/mTOR network for treatment of leukemia.Cellular and molecular life sciences : CMLS · 2015Review
- Phosphorylation of c-Cbl and p85 PI3K driven by all-trans retinoic acid and CD38 depends on Lyn kinase activity.Cellular signalling · 2014Article
- Combined staurosporine and retinoic acid induces differentiation in retinoic acid resistant acute promyelocytic leukemia cell lines.Scientific reports · 2014Article
- Mesenchymal stem cells induce granulocytic differentiation of acute promyelocytic leukemic cells via IL-6 and MEK/ERK pathways.Stem cells and development · 2013Article
- Retinoid-regulated FGF8f secretion by osteoblasts bypasses retinoid stimuli to mediate granulocytic differentiation of myeloid leukemia cells.Molecular cancer therapeutics · 2012Article
- Combined inhibition of PI3K and mTOR exerts synergistic antiproliferative effect, but diminishes differentiative properties of rapamycin in acute myeloid leukemia cells.Pathology oncology research : POR · 2011Article
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Authors and funding
6 authors at 1 institution in 1 country.
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No grant is acknowledged in the PubMed record.
Abstract
purposeIn acute promyelocytic leukemia (APL) the chromosome translocation t(15;17) resulting in the PML-RAR alpha fusion protein is responsible for a blockage of myeloid differentiation. In this study we investigated the expression of different Phosphatidylinositol 3-kinase (PI3K) isoforms during granulocyte differentiation of NB4 cells induced by all-trans-retinoic acid (ATRA), 9-cis-retinoic acid (9cisRA) or retinoic acid receptor (RAR) agonists.
methodsNB4 cells were analysed for their ability to differentiate into granulocytic lineage by the use of ATRA, 9cisRA or RAR agonists. Expression of signalling proteins was investigated by western blot and real-time PCR. PI3K activity was determined by in vitro kinase assays.
resultsCo-treatment of NB4 cells with either LY294002 to inhibit PI3Ks or PD98059 in order to suppress MEK activity led to significant reduction of CD11b surface expression during ATRA, 9cisRA or the RAR alpha agonist Ro40-6055 dependent NB4 cells granulocyte differentiation. We also show that only the G-protein coupled receptor activated PI3Kgamma isoform demonstrates up-regulated protein and mRNA expression during myeloid differentiation of NB4 cells via RAR alpha and RAR beta-dependent mechanism. Furthermore, activation of MAPK cascade including phosphorylation of MEK increases during retinoid induced differentiation of NB4 cells. Interestingly, protein kinase assays of immunoprecipitated PI3Kgamma revealed a protein of about 50 kDa that is phosphorylated when NB4 cells were treated with the RAR alpha agonist Ro40-6055.
conclusionCollectively, our data suggest additive effects of PI3K and MAPK activity on ATRA-dependent NB4 cells granulocyte differentiation.
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