Protein Kinase Cι Activity Is Necessary for Bcr-Abl-mediated Resistance to Drug-induced Apoptosis

Jamieson, Lee; Carpenter, Lee; Biden, Trevor J.; Fields, Alan P.

doi:10.1074/jbc.274.7.3927

Cited by 107 publications

(137 citation statements)

References 30 publications

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“…Furthermore, PKC contributes to Bcr-Abl-mediated drug resistance. 127 Induction of PKC protects from Fas-mediated apoptosis in viral infected T cells. 128 PKC is critical for NF-B activation, by inducing dissociation from I B.…”

Section: Pkc and Multidrug Resistancementioning

confidence: 99%

Molecular signals in anti-apoptotic survival pathways

O'Gorman

Cotter

2001

Leukemia

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Drug resistance, to date, has primarily been attributed to increased drug export or detoxification mechanisms. Despite correlations between drug export and drug resistance, it is increasingly apparent that such mechanisms cannot fully account for chemoresistance in neoplasia. It is now widely accepted that chemotherapeutic drugs kill tumour cells by inducing apoptosis, a genetically regulated cell death programme. Evidence is emerging that the exploitation of survival pathways, which may have contributed to disease development in the first instance, may also be important in the development of the chemoresistance. This review discusses the components of and associations between multiple signalling cascades and their possible contribution to the development of neoplasia and the chemoresistant phenotype. Leukemia (2001) 15, 21-34.

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Section: Pkc and Multidrug Resistancementioning

confidence: 99%

Molecular signals in anti-apoptotic survival pathways

O'Gorman

Cotter

2001

Leukemia

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“…Several intracellular proteins may inhibit apoptosis by interfering with death receptor signal transduction either at the DISC (FLIPs) (Irmler et al, 1997;Leverkus et al, 2000) or mitochondrial (Bcl-2, Bcl-x L ) level (Reed, 1998). Protein kinase C (PKC) has been shown to regulate apoptosis induced by various stimuli (Sca di et al, 1999;Jamieson et al, 1999;Sawai et al, 1997;Kobayashi et al, 1997). Furthermore, it has been demonstrated that stimulation of CD95 selectively inhibits certain PKC-isoforms in CD95-sensitive Jurkat T cells (Chen and Faller, 1999).…”

Section: Introductionmentioning

confidence: 99%

CD95 and TRAIL receptor-mediated activation of protein kinase C and NF-κB contributes to apoptosis resistance in ductal pancreatic adenocarcinoma cells

et al. 2001

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The molecular alterations in tumour cells leading to resistance towards apoptosis induced by CD95 and TRAIL-receptors are not fully understood. We report here that the stimulation of the CD95-and TRAILresistant human pancreatic adenocarcinoma cell line PancTuI with an agonistic anti-CD95 antibody or TRAIL resulted in activation of protein kinase C and NF-kB. Inhibition of protein kinase C by GoÈ 6983 sensitized these cells to apoptotic challenges and strongly diminished activation of NF-kB by anti-CD95 and TRAIL. Similarly, inhibition of NF-kB by MG132 or by transient transfection with a dominant negative mutant of IkBa restored the responsiveness of PancTuI cells to both death ligands. In the CD95 and TRAILsensitive cell line Colo357 the induction of protein kinase C and NF-kB following activation of CD95 and TRAIL-R was very moderate compared with PancTuI cells. However, pre-incubation of these cells with PMA strongly reduced their apoptotic response to anti-CD95 and TRAIL. Taken together, we show that activation of protein kinase C operates directly in a death receptordependent manner in PancTuI cells and protect pancreatic tumour cells from anti-CD95 and TRAILmediated apoptosis by preventing the loss DCm and Cytochrome c release as well as by induction of NF-kB. Oncogene (2001) 20, 4258 ± 4269.

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“…Several investigators have implicated PKC and Bcl-Xl as playing at least a partial role in BCR/ABL-mediated drug resistance. 13,17 The BCR/ABL fusion protein is present in virtually all CML patient tumor specimens and appears to be the initial transforming event. Because of these findings BCR/ABL is an attractive target for the development of potential inhibitors of this constuitively active non-receptor tyrosine kinase.…”

Section: Introductionmentioning

confidence: 99%

“…10,11 The p210 bcr-abl fusion protein is a constitutively active tyrosine kinase that is also believed to be the main contributor to the inherent resistance of CML cells to almost every chemotherapeutic agent. [12][13][14][15] Antisense oligonucleotides targeted to the BCR/ABL gene have been shown to cause increased apoptosis and the loss of the multidrug-resistant phenotype in K562 CML cells. 12,16 The exact mechanism of BCR/ABL-mediated drug resistance is not entirely clear and most likely is multi-factorial.…”

Section: Introductionmentioning

confidence: 99%