p53-Dependent cell cycle control: response to genotoxic stress

Schwartz, Dov; Rotter, Varda

doi:10.1006/scbi.1998.0095

Cited by 185 publications

(103 citation statements)

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“…5-10 µg of ∆Np63-coupled beads were incubated with 300 µg total protein of Saos-2 cells expressing control (lanes 1 and 2), RACK1 (lanesdamage, the p53 protein levels are dramatically increased and, in turn mediate cell cycle arrest or apoptosis. 4,[35][36][37][38][39]50 Response to chemotherapeutic agents in malignant tumors depends on many factors, most of which are as yet unknown. The molecular mechanism implicated in this response is thought to be through DNA damage and subsequent overexpression and stabilization of p53, which then induces apoptosis or cell cycle arrest.…”

Section: Discussionmentioning

confidence: 99%

RACK1 and Stratifin Target ΔNp63α for a Proteasome Degradation in Head and Neck Squamous Cell Carcinoma Cells upon DNA Damage

Fomenkov¹,

Zangen²,

Huang³

et al. 2004

Cell Cycle

117

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Section: Discussionmentioning

confidence: 99%

RACK1 and Stratifin Target ΔNp63α for a Proteasome Degradation in Head and Neck Squamous Cell Carcinoma Cells upon DNA Damage

Fomenkov¹,

Zangen²,

Huang³

et al. 2004

Cell Cycle

117

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“…Activities of p53 are intricately linked to MT induction and localisation. p53 causes cell cycle arrest at G1 in response to low levels of stress (Schwartz and Rotter, 1998), and studies have shown localisation of MT in the nucleus occurs during G1/S phase when the requirement for zinc is highest (Cherian and Apostolova, 2000). p53 initiates apoptosis during high levels of stress (Schwartz and Rotter, 1998), and MT has been shown to play a role in different aspects of apoptosis.…”

Section: Discussionmentioning

confidence: 99%

“…p53 causes cell cycle arrest at G1 in response to low levels of stress (Schwartz and Rotter, 1998), and studies have shown localisation of MT in the nucleus occurs during G1/S phase when the requirement for zinc is highest (Cherian and Apostolova, 2000). p53 initiates apoptosis during high levels of stress (Schwartz and Rotter, 1998), and MT has been shown to play a role in different aspects of apoptosis. Further evidence is provided by a recent study showing that cadmium can affect the stability and DNAbinding activity of p53 (Méplan et al, 1999).…”

Section: Discussionmentioning

confidence: 99%

“…p53 is able to respond to different cellular stresses such as DNA damage, hypoxia, oxidative stress, and oncogene activation. Upon activation, p53 initiates a number of cellular activities that can ultimately culminate in G1 or G2 cell cycle arrest and DNA repair, apoptosis, or other cellular changes (Schwartz and Rotter, 1998). As a critical cellular mediator of the response to genotoxic damage, P53 has a direct role in maintaining the integrity of the genome.…”

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confidence: 99%

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Potential role of p53 on metallothionein induction in human epithelial breast cancer cells

Fan

Cherian

2002

Br J Cancer

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The expression and induction of metallothionein has been associated with protection against oxidative stress and apoptosis. This study examines the effect of tumour suppressor protein p53 on metallothionein expression following CdCl 2 treatment in eight human epithelial breast cancer cell lines differing in p53 and oestrogen-receptor status. Cells were treated with 10 mM CdCl 2 for 24 h and metallothionein protein levels were measured by cadmium binding assay. MCF7 cells which are p53-positive (p53+) and oestrogen-receptor-positive showed a large induction in metallothionein synthesis by 10.79+1.36-fold. Other breast cancer cell lines which are p53-negative (p537) and oestrogen-receptor-negative or weakly oestrogenreceptor-positive showed a small induction ranging from 1.40+0.10 to 3.65+0.30-fold. RT -PCR analysis showed an induction of metallothionein mRNA in MCF7 cells by about 1.61+0.08-fold, while in HCC1806 cells (p537, oestrogenreceptor-negative) by 1.11+0.13-fold, and in MDA-MB-231 (p537, oestrogen-receptor-negative) by 1.25+0.06-fold. Metallothionein localisation was determined by immunohistochemical staining. Prior to metal treatment, metallothionein was localised mainly in the cytoplasm of MCF7 and MDA-MB-231 cells. After treatment with 10 mM CdCl 2 for 24 h, MCF7 cells showed intense nuclear and cytoplasmic staining for metallothionein, while MDA-MB-231 cells showed staining in the cytoplasm with weak nuclear staining. Apoptosis induced by 10 -40 mM CdCl 2 at time points between 4 and 48 h was examined with TUNEL assay. In MCF7 cells, apoptosis increased with higher concentrations of CdCl 2 , it peaked at 6 -8 h and appeared again at 48 h for all concentrations of CdCl 2 tested. In MDA-MB-231 cells, apoptosis remained at low levels for 10 -40 mM CdCl 2 at all time points. Studies on cadmium uptake showed similar uptake and accumulation of cadmium at 8 and 24 h in all the cell lines. The data demonstrate that treatment of epithelial breast cancer cells with 10 mM CdCl 2 for 24 h caused a greater induction of metallothionein protein and mRNA expression in p53+ and oestrogen-receptor-positive cells as compared to p537 and oestrogen-receptor-negative or weakly oestrogen-receptor-positive cells. This effect may be associated with the occurrence of apoptosis and suggests a role for p53 and oestrogen-receptor on the expression and induction of metallothionein in epithelial cells.

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“…The activation of the tumor suppressor protein p53 plays an important, though not essential, role in the activation of the responses of the genotoxic stress pathways (Schartz and Rotter, 1998). The activation of p53 may even provide a means to distinguish the consequences of genotoxic dsDNA break induction from less-toxic ssDNA break formation (Nelson and Kastan, 1994).…”

Section: Topotecan Causes the Multipoint Slowing Of Cell Cycle Travermentioning

confidence: 99%

Tracking the cell cycle origins for escape from topotecan action by breast cancer cells

et al. 2003

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The anticancer agent topotecan is considered to be S-phase specific. This implies that cancer cells that are not actively replicating DNA could resist the effects of the drug. The cycle specificity of topotecan action was investigated in MCF-7 cells, using time-lapse microscopy to link the initial cell cycle position during acute exposures to topotecan with the antiproliferative consequences for individual cells. The bioactive dose range (0.5 -10 mM) for 1-h topotecan exposures was defined by rapid drug delivery and topoisomerase I trapping. Topotecan caused pan-cycle induction and activation of p53. Lineage analysis of the time-lapse sequences identified cells initially in S-phase and G2, and defined the time to mitosis for cells originating from G2, S-phase and G1. Topotecan prevented all mitoses from S-phase cells and G1 cells (half-maximal effects at 0.14 mM and 0.96 mM, respectively). No dose of topotecan completely prevented mitosis among G2 cells, and at saturating doses of topotecan about half the cells of G2 origin continued dividing (the half-maximal effects was at 0.31 mM). Overall, topotecan differentially targeted G1-, S-and G2-phase cells, but many G2 cells were resistant to topotecan, presenting a clear route for cell cycle-mediated drug resistance.

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p53-Dependent cell cycle control: response to genotoxic stress

Cited by 185 publications

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RACK1 and Stratifin Target ΔNp63α for a Proteasome Degradation in Head and Neck Squamous Cell Carcinoma Cells upon DNA Damage

RACK1 and Stratifin Target ΔNp63α for a Proteasome Degradation in Head and Neck Squamous Cell Carcinoma Cells upon DNA Damage

Potential role of p53 on metallothionein induction in human epithelial breast cancer cells

Tracking the cell cycle origins for escape from topotecan action by breast cancer cells

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p53-Dependent cell cycle control: response to genotoxic stress

Cited by 185 publications

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RACK1 and Stratifin Target &Delta;Np63&alpha; for a Proteasome Degradation in Head and Neck Squamous Cell Carcinoma Cells upon DNA Damage

RACK1 and Stratifin Target &Delta;Np63&alpha; for a Proteasome Degradation in Head and Neck Squamous Cell Carcinoma Cells upon DNA Damage

Potential role of p53 on metallothionein induction in human epithelial breast cancer cells

Tracking the cell cycle origins for escape from topotecan action by breast cancer cells

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Product

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RACK1 and Stratifin Target ΔNp63α for a Proteasome Degradation in Head and Neck Squamous Cell Carcinoma Cells upon DNA Damage

RACK1 and Stratifin Target ΔNp63α for a Proteasome Degradation in Head and Neck Squamous Cell Carcinoma Cells upon DNA Damage