scholarly journals Restoration of endogenous wild-type p53 activity in a glioblastoma cell line with intrinsic temperature-sensitive p53 induces growth arrest but not apoptosis

2001 ◽  
Vol 94 (1) ◽  
pp. 35-43 ◽  
Author(s):  
Jun Ikeda ◽  
Mitsuhiro Tada ◽  
Nobuaki Ishii ◽  
Hideyuki Saya ◽  
Kazuhiko Tsuchiya ◽  
...  
Keyword(s):  
Cell Line ◽  
Growth Arrest ◽  
Temperature Sensitive ◽  
Glioblastoma Cell Line ◽  
Glioblastoma Cell ◽  
Wild Type ◽  
Wild Type P53

scholarly journals Inhibition of p53-mediated growth arrest by overexpression of cyclin-dependent kinases.

1996 ◽  
Vol 16 (8) ◽  
pp. 4445-4455 ◽  
Author(s):  
K M Latham ◽  
S W Eastman ◽  
A Wong ◽  
P W Hinds
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Progression ◽  
Growth Arrest ◽  
Temperature Sensitive ◽  
Wild Type ◽  
Aberrant Expression ◽  
Cycle Progression ◽  
Cyclin Dependent Kinases ◽  
Rat Fibroblasts ◽  
Wild Type P53

Rat fibroblasts transformed by a temperature-sensitive mutant of murine p53 undergo a reversible growth arrest in G1 at 32.5 degrees C, the temperature at which p53 adopts a wild-type conformation. The arrested cells contain inactive cyclin-dependent kinase 2 (cdk2) despite the presence of high levels of cyclin E and cdk-activating kinase activity. This is due in part to p53-dependent expression of the p2l cdk inhibitor. Upon shift to 39 degrees C, wild-type p53 is lost and cdk2 activation and pRb phosphorylation occur concomitantly with loss of p2l. This p53-mediated growth arrest can be abrogated by overexpression of cdk4 and cdk6 but not cdk2 or cyclins, leading to continuous proliferation of transfected cells in the presence of wild-type p53 and p2l. Kinase-inactive counterparts of cdk4 and cdk6 also rescue these cells from growth arrest, implicating a noncatalytic role for cdk4 and cdk6 in this resistance to p53-mediated growth arrest. Aberrant expression of these cell cycle kinases may thus result in an oncogenic interference with inhibitors of cell cycle progression.

scholarly journals Accumulation of p53 in a mutant cell line defective in the ubiquitin pathway.

1994 ◽  
Vol 14 (3) ◽  
pp. 1997-2003 ◽  
Author(s):  
D R Chowdary ◽  
J J Dermody ◽  
K K Jha ◽  
H L Ozer
Keyword(s):  
Cell Line ◽  
Mutant Cell ◽  
P53 Gene ◽  
Mouse Cell ◽  
Temperature Sensitive ◽  
Restrictive Temperature ◽  
Wild Type ◽  
Proteolytic Pathway ◽  
Ubiquitination Pathway ◽  
Wild Type P53

The wild-type p53 gene product plays an important role in the control of cell proliferation, differentiation, and survival. Altered function is frequently associated with changes in p53 stability. We have studied the role of the ubiquitination pathway in the degradation of p53, utilizing a temperature-sensitive mutant, ts20, derived from the mouse cell line BALB/c 3T3. We found that wild-type p53 accumulates markedly because of decreased breakdown when cells are shifted to the restrictive temperature. Introduction of sequences encoding the human ubiquitin-activating enzyme E1 corrects the temperature sensitivity defect in ts20 and prevents accumulation of p53. The data therefore strongly indicate that wild-type p53 is degraded intracellularly by the ubiquitin-mediated proteolytic pathway.

scholarly journals Concerted Regulation of Wild-Type p53 Nuclear Accumulation and Activation by S100B and Calcium-Dependent Protein Kinase C

1999 ◽  
Vol 19 (10) ◽  
pp. 7168-7180 ◽  
Author(s):  
Christian Scotto ◽  
Christian Delphin ◽  
Jean Christophe Deloulme ◽  
Jacques Baudier
Keyword(s):  
Nuclear Translocation ◽  
Growth Arrest ◽  
Nuclear Accumulation ◽  
Temperature Sensitive ◽  
Checkpoint Control ◽  
Wild Type ◽  
Calcium Dependent ◽  
Mouse Embryo Fibroblasts ◽  
Wild Type P53 ◽  
Embryo Fibroblasts

ABSTRACT The calcium ionophore ionomycin cooperates with the S100B protein to rescue a p53-dependent G1 checkpoint control in S100B-expressing mouse embryo fibroblasts and rat embryo fibroblasts (REF cells) which express the temperature-sensitive p53Val135 mutant (C. Scotto, J. C. Deloulme, D. Rousseau, E. Chambaz, and J. Baudier, Mol. Cell. Biol. 18:4272–4281, 1998). We investigated in this study the contributions of S100B and calcium-dependent PKC (cPKC) signalling pathways to the activation of wild-type p53. We first confirmed that S100B expression in mouse embryo fibroblasts enhanced specific nuclear accumulation of wild-type p53. We next demonstrated that wild-type p53 nuclear translocation and accumulation is dependent on cPKC activity. Mutation of the five putative cPKC phosphorylation sites on murine p53 into alanine or aspartic residues had no significant effect on p53 nuclear localization, suggesting that the cPKC effect on p53 nuclear translocation is indirect. A concerted regulation by S100B and cPKC of wild-type p53 nuclear translocation and activation was confirmed with REF cells expressing S100B (S100B-REF cells) overexpressing the temperature-sensitive p53Val135 mutant. Stimulation of S100B-REF cells with the PKC activator phorbol ester phorbol myristate acetate (PMA) promoted specific nuclear translocation of the wild-type p53Val135 species in cells positioned in early G1 phase of the cell cycle. PMA also substituted for ionomycin in the mediating of p53-dependent G1 arrest at the nonpermissive temperature (37.5°C). PMA-dependent growth arrest was linked to the cell apoptosis response to UV irradiation. In contrast, growth arrest mediated by a temperature shift to 32°C protected S100B-REF cells from apoptosis. Our results suggest a model in which calcium signalling, linked with cPKC activation, cooperates with S100B to promote wild-type p53 nuclear translocation in early G1 phase and activation of a p53-dependent G1checkpoint control.

scholarly journals Accumulation of p53 in a mutant cell line defective in the ubiquitin pathway

1994 ◽  
Vol 14 (3) ◽  
pp. 1997-2003
Author(s):  
D R Chowdary ◽  
J J Dermody ◽  
K K Jha ◽  
H L Ozer
Keyword(s):  
Cell Line ◽  
Mutant Cell ◽  
P53 Gene ◽  
Mouse Cell ◽  
Temperature Sensitive ◽  
Restrictive Temperature ◽  
Wild Type ◽  
Proteolytic Pathway ◽  
Ubiquitination Pathway ◽  
Wild Type P53

The wild-type p53 gene product plays an important role in the control of cell proliferation, differentiation, and survival. Altered function is frequently associated with changes in p53 stability. We have studied the role of the ubiquitination pathway in the degradation of p53, utilizing a temperature-sensitive mutant, ts20, derived from the mouse cell line BALB/c 3T3. We found that wild-type p53 accumulates markedly because of decreased breakdown when cells are shifted to the restrictive temperature. Introduction of sequences encoding the human ubiquitin-activating enzyme E1 corrects the temperature sensitivity defect in ts20 and prevents accumulation of p53. The data therefore strongly indicate that wild-type p53 is degraded intracellularly by the ubiquitin-mediated proteolytic pathway.

Establishment and Characterization of a Human Glioblastoma Cell Line Which Expresses Somatostatin and its Functional Receptor

1999 ◽  
Vol 11 (3) ◽  
pp. 215-222
Author(s):  
Nobuo HIROTA ◽  
Kiyoshi MATSUMOTO ◽  
Shigeki SUNAGA ◽  
Masataka IIDA ◽  
Hiroshi SAKAGAMI ◽  
...  
Keyword(s):  
Cell Line ◽  
Glioblastoma Cell Line ◽  
Glioblastoma Cell ◽  
Human Glioblastoma ◽  
Human Glioblastoma Cell Line ◽  
Human Glioblastoma Cell ◽  
Functional Receptor

scholarly journals Enhanced Anti-Tumor Activity in Mice with Temozolomide-Resistant Human Glioblastoma Cell Line-Derived Xenograft Using SN-38-Incorporated Polymeric Microparticle

2021 ◽  
Vol 22 (11) ◽  
pp. 5557
Author(s):  
Tao-Chieh Yang ◽  
Shih-Jung Liu ◽  
Wei-Lun Lo ◽  
Shu-Mei Chen ◽  
Ya-Ling Tang ◽  
...  
Keyword(s):  
Cell Line ◽  
Therapeutic Index ◽  
Glioblastoma Cell Line ◽  
Glioblastoma Cell ◽  
Human Glioblastoma ◽  
Human Glioblastoma Cell Line ◽  
Human Glioblastoma Cell ◽  
Therapeutic Benefits ◽  
Biodegradable Poly ◽  
Anti Tumor Activity

Glioblastoma multiforme (GBM) has remained one of the most lethal and challenging cancers to treat. Previous studies have shown encouraging results when irinotecan was used in combination with temozolomide (TMZ) for treating GBM. However, irinotecan has a narrow therapeutic index: a slight dose increase in irinotecan can induce toxicities that outweigh its therapeutic benefits. SN-38 is the active metabolite of irinotecan that accounts for both its anti-tumor efficacy and toxicity. In our previous paper, we showed that SN-38 embedded into 50:50 biodegradable poly[(d,l)-lactide-co-glycolide] (PLGA) microparticles (SMPs) provides an efficient delivery and sustained release of SN-38 from SMPs in the brain tissues of rats. These properties of SMPs give them potential for therapeutic application due to their high efficacy and low toxicity. In this study, we tested the anti-tumor activity of SMP-based interstitial chemotherapy combined with TMZ using TMZ-resistant human glioblastoma cell line-derived xenograft models. Our data suggest that treatment in which SMPs are combined with TMZ reduces tumor growth and extends survival in mice bearing xenograft tumors derived from both TMZ-resistant and TMZ-sensitive human glioblastoma cell lines. Our findings demonstrate that combining SMPs with TMZ may have potential as a promising strategy for the treatment of GBM.

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