Comparative microarray analysis of gene expression during apoptosis-induction by growth factor deprivation or protein kinase C inhibition

Brachat, Arndt; Pierrat, Benoı̂t; Brüngger, Adrian; Heim, Jutta

doi:10.1038/sj.onc.1203882

Cited by 32 publications

(27 citation statements)

References 78 publications

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“…These results suggest that activation of PKC␦ is necessary for the radiation-induced progression of apoptotic cell death in non-small cell lung cancer cells and that PKC␦ is located upstream of Rac1-p38 MAPK signaling in response to radiation. In line with this observation, overexpression of PKC␦ in prostate cancer cells was shown to markedly enhance the apoptosis-inducing effect (49,50). Our previous report also demonstrated that PKC␦ overexpression increased radiosensitivity in normal fibroblasts through Rac1-p38 MAPK signaling pathway (51).…”

Section: Discussionsupporting

confidence: 57%

Activation of Bak and Bax through c-Abl-Protein Kinase Cδ-p38 MAPK Signaling in Response to Ionizing Radiation in Human Non-small Cell Lung Cancer Cells

Choi

Kim

Kang

et al. 2006

Journal of Biological Chemistry

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Section: Discussionsupporting

confidence: 57%

Activation of Bak and Bax through c-Abl-Protein Kinase Cδ-p38 MAPK Signaling in Response to Ionizing Radiation in Human Non-small Cell Lung Cancer Cells

Choi

Kim

Kang

et al. 2006

Journal of Biological Chemistry

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“…CPT1A expression was enhanced during death induced by cytokine withdrawal in several hematopoietic cell lines, and therefore ␤-oxidation was proposed to function in apoptosis (48,49). More recently, differential regulation of CPT1A expression and ␤-oxidation was identified as a marker discriminating between Th1-and Th2-mediated macrophage activation (50).…”

Section: Discussionmentioning

confidence: 99%

Phosphatidylinositol 3-Kinase-dependent Modulation of Carnitine Palmitoyltransferase 1A Expression Regulates Lipid Metabolism during Hematopoietic Cell Growth

DeBerardinis

Lum

Thompson

2006

Journal of Biological Chemistry

201

163

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An abundant supply of extracellular nutrients is believed to be sufficient to suppress catabolism of cellular macromolecules. Here we show that, despite abundant extracellular nutrients, interleukin-3-deprived hematopoietic cells begin to catabolize intracellular lipids. Constitutive Akt activation blunts the increased ␤-oxidation that accompanies growth factor withdrawal, and in growth factor-replete cells, phosphatidylinositol 3-kinase (PI3K) signaling is required to suppress lipid catabolism. Surprisingly, PI3K and Akt exert these effects by suppressing expression of the ␤-oxidation enzyme carnitine palmitoyltransferase 1A (CPT1A). Cells expressing a short hairpin RNA against CPT1A fail to induce ␤-oxidation in response to growth factor withdrawal and are unable to survive glucose deprivation. When CPT1A is constitutively expressed, growth factor stimulation fails to repress ␤-oxidation. As a result, both net lipid synthesis and cell proliferation are diminished. Together, these results demonstrate that modulation of CPT1A expression by PI3K-dependent signaling is the major mechanism by which cells suppress ␤-oxidation during anabolic growth.Single-cell eukaryotes like yeast autonomously regulate their uptake of nutrients from the extracellular environment. In such organisms, cellular metabolism is regulated primarily in response to nutrient availability (1). In contrast, it has been proposed that mammalian cells do not take up and metabolize nutrients without instruction from extracellular signals. These signals, which include cytokines and other lineage-specific growth factors, stimulate signal transduction pathways that orchestrate cellular metabolism through effects on gene expression and enzyme kinetics. Together, these signal-induced changes function to direct uptake and utilization of nutrients, channeling metabolites into biosynthetic pathways (2-4). One important example of this phenomenon occurs during lymphocyte stimulation, where receptor-induced signaling directly increases glucose transport, glycolysis, lactate production, and synthesis of lipids (5-9).Many of the metabolic changes elicited by growth factors result from activation of the phosphatidylinositol 3-kinase (PI3K)/Akt 4 signaling system. In this pathway, binding of a growth factor to its surface receptor induces activation of the lipid kinase PI3K, which phosphorylates phosphatidylinositol species (10). End products of PI3K activity recruit the serine/ threonine kinase Akt to the plasma membrane where it becomes a substrate for phosphorylation and activation by phosphoinositide-dependent protein kinase 1 and other regulatory kinases (10). The metabolic effects of growth factorinduced PI3K/Akt stimulation include increases in glucose import and glycolysis, which fuel the bioenergetic and biosynthetic activities of growing cells (11-13). Constitutive activation of PI3K and/or Akt through a variety of genetic mechanisms is a common transforming event in human cancer, including some 25% of breast carcinoma and 30% of colon carcinoma (14 -1...

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“…We found that responses to growth factor removal and inhibition of protein kinase C with staurosporine shared a significant number of regulatory events (Brachat et al, 2000). In the present study we extended the investigation of drug treatment responses by analysing expression patterns of FL5.12 pro-B cells upon addition of cisplatin, camptothecin, methotrexate or paclitaxel respectively.…”

Section: Gene Expression Analysis By Cdna Microarraysmentioning

confidence: 80%

“…We selected nine candidate genes for testing their influence on proliferation and cell death kinetics. Candidates were chosen if they were not previously known to have a role in pro-B cell apoptosis and if they were differentially expressed as a consequence of at least three apoptotic stimuli, including IL-3 deprivation and staurosporine treatment (Brachat et al, 2000).…”

Section: Selection Of Candidate Genesmentioning

confidence: 99%

“…With the advent of genome-scale experimental setups it is now becoming possible to look at cellular pathways from a perspective that allows the discovery of many new, and often surprising, players and interconnections between pathways (Amundson et al, 1999;Brachat et al, 2000). One of the major challenges accompanying large-scale experiments such as gene expression profiling with DNA microarrays (Schena et al, 1995(Schena et al, , 1996 is to distinguish between central players with a direct, causative influence on the phenotypic outcome of a stimulus and unrelated side effects.…”

Section: Introductionmentioning

confidence: 99%

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A microarray-based, integrated approach to identify novel regulators of cancer drug response and apoptosis

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Comparative microarray analysis of gene expression during apoptosis-induction by growth factor deprivation or protein kinase C inhibition

Cited by 32 publications

References 78 publications

Activation of Bak and Bax through c-Abl-Protein Kinase Cδ-p38 MAPK Signaling in Response to Ionizing Radiation in Human Non-small Cell Lung Cancer Cells

Activation of Bak and Bax through c-Abl-Protein Kinase Cδ-p38 MAPK Signaling in Response to Ionizing Radiation in Human Non-small Cell Lung Cancer Cells

Phosphatidylinositol 3-Kinase-dependent Modulation of Carnitine Palmitoyltransferase 1A Expression Regulates Lipid Metabolism during Hematopoietic Cell Growth

A microarray-based, integrated approach to identify novel regulators of cancer drug response and apoptosis

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