Analysis of cyclin B1 and CDK activity during apoptosis induced by camptothecin treatment

Borgne, Annie; Versteege, Isabella; Mahé, Maxime M.; Studény, Aurélie; Léonce, Stéphane; Naime, Isabelle; Rodriguez, Marianne; Hickman, John A.; Meijer, Laurent; Golsteyn, Roy M.

doi:10.1038/sj.onc.1209718

Cited by 37 publications

(25 citation statements)

References 53 publications

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“…Intriguingly, S181A tumors showed higher cyclin B1 expression than the others (Fig. 1D) in line with the requirement of increased cyclin B1 for apoptosis induction previously reported in several tumor cell lines (17)(18)(19). Moreover, cyclin B1 overexpression has already been related to the mild transforming phenotype of codon 13 KRAS mutations in NIH3T3 models (16).…”

Section: Resultssupporting

confidence: 65%

Phosphorylation at Ser-181 of Oncogenic KRAS Is Required for Tumor Growth

et al. 2014

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KRAS phosphorylation has been reported recently to modulate the activity of mutant KRAS protein in vitro. In this study, we defined S181 as a specific phosphorylation site required to license the oncogenic function of mutant KRAS in vivo. The phosphomutant S181A failed to induce tumors in mice, whereas the phosphomimetic mutant S181D exhibited an enhanced tumor formation capacity, compared with the wild-type KRAS protein. Reduced growth of tumors composed of cells expressing the nonphosphorylatable KRAS S181A mutant was correlated with increased apoptosis. Conversely, increased growth of tumors composed of cells expressing the phosphomimetic KRAS S181D mutant was correlated with increased activation of AKT and ERK, two major downstream effectors of KRAS. Pharmacologic treatment with PKC inhibitors impaired tumor growth associated with reduced levels of phosphorylated KRAS and reduced effector activation. In a panel of human tumor cell lines expressing various KRAS isoforms, we showed that KRAS phosphorylation was essential for survival and tumorigenic activity. Furthermore, we identified phosphorylated KRAS in a panel of primary human pancreatic tumors. Taken together, our findings establish that KRAS requires S181 phosphorylation to manifest its oncogenic properties, implying that its inhibition represents a relevant target to attack KRAS-driven tumors. Cancer Res; 74(4);

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Section: Resultssupporting

confidence: 65%

Phosphorylation at Ser-181 of Oncogenic KRAS Is Required for Tumor Growth

et al. 2014

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“…This was accompanied by an increase in the expression of cyclin B1 and cyclin E2 in these cells. siRNA-mediated inhibition of cyclin B1 prevented the cells from undergoing apoptosis, whereas siRNA-targeting of cyclin E2 had no effect (Borgne et al, 2006). Thus, cyclin B1 expression is required for apoptotic induction by camptothecin in HT29 cells.…”

Section: Pro-and Anti-apoptotic Effects Of Cyclinsmentioning

confidence: 89%

“…Interestingly, targeting of cyclin B1 by siRNA in primary human vascular endothelial cells (HUVECS), does not decrease their proliferation . Camptothecin treatment of HT29 cells induced apoptosis (Banerji and Los, 2006;Borgne et al, 2006;Huang et al, 2006). This was accompanied by an increase in the expression of cyclin B1 and cyclin E2 in these cells.…”

Section: Pro-and Anti-apoptotic Effects Of Cyclinsmentioning

confidence: 96%

Cell survival, cell death and cell cycle pathways are interconnected: Implications for cancer therapy

Maddika¹,

Ande²,

Panigrahi³

et al. 2007

Drug Resistance Updates

411

302

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The partial cross-utilization of molecules and pathways involved in opposing processes like cell survival, proliferation and cell death, assures that mutations within one signaling cascade will also affect the other opposite process at least to some extent, thus contributing to homeostatic regulatory circuits. This review highlights some of the connections between opposite-acting pathways. Thus, we discuss the role of cyclins in the apoptotic process, and in the regulation of cell proliferation. CDKs and their inhibitors like the INK4-family (p16 Ink4a , p15 Ink4b , p18 Ink4c , p19 Ink4d ), and the Cip1/Waf1/Kip1-2-family (p21 Cip1/Waf1 , p27 Kip1 , p57 Kip2 ) are shown both in the context of proliferation regulators and as contributors to the apoptotic machinery. Bcl2-family members (i.e. Bcl2, Bcl-X L Mcl-1 L ; Bax, Bok/Mtd, Bak, and Bcl-X S ; Bad, Bid, Bim EL , Bmf, Mcl-1 S ) are highlighted both for their apoptosis-regulating capacity and also for their effect on the cell cycle progression. The PI3-K/Akt cell survival pathway is shown as regulator of cell metabolism and cell survival, but examples are also provided where aberrant activity of the pathway may contribute to the induction of apoptosis. Myc/Mad/Max proteins are shown both as a powerful S-phase driving complex and as apoptosis-sensitizers. We also discuss multifunctional proteins like p53 and Rb (RBL1/p107, RBL2/p130) both in the context of G 1 -S transition and as apoptotic triggers. Finally, we reflect on novel therapeutic approaches that would involve redirecting over-active survival and proliferation pathways towards induction of apoptosis in cancer cells.

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“…In accord with that, it has been shown that nuclear accumulation of cyclin B1 is one of the factors involved in triggering this kind of cell death, as it was found mainly in the cytoplasm of the cells that were apoptotic-resistant and accumulated in the nucleus of the apoptotic-prone ones [27]. Moreover, it has been proven that targeting cyclin B1 protein by RNAi or chemical inhibitors leads to decreased number of apoptotic HT29 cells after treatment with camptothecin [23]. On the other hand, reduction of cyclin B1 level may also induce cell cycle arrest and apoptosis in some cancer cells [28].…”

Section: Discussionmentioning

confidence: 59%

“…One of the causes of mitotic catastrophe execution may be premature entry into mitosis before the completion of DNA replication, which results in abnormal organization of chromosomes in the presence of the high activity of cyclin B1/Cdk1 complex in the nucleus area [11,23]. There are suggestions that such an aberrant mitosis is mediated by Notch inhibition followed by NF-kB activity, which in turn induces high levels of cyclin B1 [24].…”

Section: Discussionmentioning

confidence: 99%

Expression of cyclin B1 after induction of senescence and cell death in non-small cell lung carcinoma A549 cells

Żuryń

Gagat

Gackowska

et al. 2012

Folia Histochem Cytobiol.

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Abstract:The purpose of this study was to evaluate the level of mitotic cyclin B1 in the context of senescence and cell death in A549 non-small cell lung carcinoma cells. This was performed through analysis of the cell cycle, the percentage of SA-b-galactosidase-positive, as well as TUNEL-positive cells. Morphological alterations were studied using a transmission electron microscope. Changes in the intracellular level and the presence of cyclin B1 in the nucleus and cytoplasm areas were detected by flow cytometry and confocal fluorescence microscopy, respectively. In the cells exposed to various concentrations of doxorubicin, different kinds of cell death and senescent phenotype were observed. Alterations in the cell cycle and increased polyploidy may be indicative of mitotic catastrophe execution. Changes in cyclin B1 may also be strictly related to its different regulation at mitotic catastrophe and senescence programs.

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Analysis of cyclin B1 and CDK activity during apoptosis induced by camptothecin treatment

Cited by 37 publications

References 53 publications

Phosphorylation at Ser-181 of Oncogenic KRAS Is Required for Tumor Growth

Phosphorylation at Ser-181 of Oncogenic KRAS Is Required for Tumor Growth

Cell survival, cell death and cell cycle pathways are interconnected: Implications for cancer therapy

Expression of cyclin B1 after induction of senescence and cell death in non-small cell lung carcinoma A549 cells

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