Apoptosis-prone phenotype of human colon carcinoma cells with a high level amplification of the c-myc gene

Donzelli, Maddalena; Bernardi, Rosa; Negri, C.; Prosperi, Ennio; Padovan, Laura; Lavialle, Christian; Brison, Olivier; Scovassi, Anna Ivana

doi:10.1038/sj.onc.1202309

Cited by 45 publications

(37 citation statements)

References 49 publications

(58 reference statements)

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“…The results we obtained on colon carcinoma cell lines showed that 2-ME interferes with HCT116 cell viability in a dose-dependent/irreversible manner, while its effect on SW613-B3 is less potent and is reversible. This different impact of 2-ME could be explained by the high intrinsic resistance of the latter cell line to a panel of drugs (Donzelli et al 1999;Bottone et al 2003;Gorrini et al 2003). However, we found that 2-ME has an inhibitory effect on cell viability of both colon carcinoma cells, thus suggesting that it could be a promising cytotoxic, anti-proliferative agent.…”

Section: Discussioncontrasting

confidence: 47%

“…It has to be taken into account that our experimental design differed from that of Carothers et al (2002), given that our analysis included the use of a second colon carcinoma cell line, i.e. the SW613-B3, which we found to be extremely drug resistant (Donzelli et al 1999;Bottone et al 2003;Gorrini et al 2003). For this reason, the concentrations of 2-ME we used (1-100 µM) were higher that those administered by Carothers et al (2002), which reached a maximum of 2.5 µM.…”

Section: Discussionmentioning

confidence: 96%

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2-Methoxyestradiol: New perspectives in colon carcinoma treatment

Parks

Tillhon

Donà

et al. 2011

Molecular and Cellular Endocrinology

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Section: Discussioncontrasting

confidence: 47%

Section: Discussionmentioning

confidence: 96%

2-Methoxyestradiol: New perspectives in colon carcinoma treatment

Parks

Tillhon

Donà

et al. 2011

Molecular and Cellular Endocrinology

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“…On the other hand, apoptosis is a well-documented consequence of c-Myc ectopic expression in cells subjected to growth factor deprivation or to hypoxia. Moreover, a correlation between high c-myc expression and apoptosis has been reported for some solid tumors (Homan and Liebermann, 1998;Alarcon et al, 1996;Donzelli et al, 1999). However, the pro-apoptotic e ect of c-Myc is at odds with the frequently found cmyc overexpression in human cancer.…”

Section: Discussionmentioning

confidence: 93%

c-Myc antagonizes the effect of p53 on apoptosis and p21WAF1 transactivation in K562 leukemia cells

et al. 2000

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c-myc protooncogene positively regulates cell proliferation and overexpression of c-myc is found in many solid tumors and leukemias. In the present study we used the K562 human myeloid leukemia cell line as a model to study the functional interaction between c-Myc and p53. Using two di erent methods, we generated K562 transfectant cell lines with conditional expression of either c-Myc or p53. The cells expressed the p53 Vall35 mutant, which adopts a wild-type conformation at 328C, while c-Myc induction was achieved with a zinc-inducible expression vector. We found that p53 in wild-type conformation induces growth arrest and apoptosis of K562. Expression of c-Myc signi®cantly attenuated apoptosis and impaired the transcriptional activity of p53 on p21 WAF1 , Bax and cytomegalovirus promoters. The impairment of p21 WAF1 transactivation by c-Myc was con®rmed by transfection of a c-Myc-estrogen receptor fusion protein and by induction of c-myc by zinc in transfected cells. Also, p53-mediated up-regulation of p21 WAF1 mRNA protein were signi®cantly reduced by cMyc, while Bax levels were una ected. Consistently, cMyc increased cyclin-dependent kinase 2 activity in K562 cells expressing p53 in wild-type conformation. These results suggest that c-Myc overexpression may antagonize the pro-apoptotic function of p53, thus providing a molecular mechanism for the frequently observed deregulation of c-myc in human cancer.

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“…Western Blot Analysis-Samples were electrophoresed in a minigel and transferred onto a nitrocellulose filter (Bio-Rad) (17). After saturation for 1 h with PTN (phosphate-buffered saline containing 0.2% Tween 20 and 10% newborn calf serum), the membrane was incubated overnight with the following mAbs: C-2-10 to PARP-1 (Alexis), diluted 1:2500 in PTN; PC10 to PCNA (Dako), diluted 1:1000; 187 to p21 (Santa Cruz Biotechnology), diluted 1:100; AE-4 to histone H1 (Santa Cruz), diluted 1:1000.…”

Section: Methodsmentioning

confidence: 99%

Human Proliferating Cell Nuclear Antigen, Poly(ADP-ribose) Polymerase-1, and p21 /

Frouin

Maga

Denegri

et al. 2003

Journal of Biological Chemistry

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We addressed the analysis of the physical and functional association of proliferating cell nuclear antigen (PCNA), a protein involved in many DNA transactions, with poly(ADP-ribose) polymerase (PARP-1), an enzyme that plays a crucial role in DNA repair and interacts with many DNA replication/repair factors. We demonstrated that PARP-1 and PCNA co-immunoprecipitated both from the soluble and the DNA-bound fraction isolated from S-phase-synchronized HeLa cells. Immunoprecipitation experiments with purified proteins further confirmed a physical association between PARP-1 and PCNA. To investigate the effect of this association on PARP-1 activity, an assay based on the incorporation of radioactive NAD was performed. Conversely, the effect of PARP-1 on PCNA-dependent DNA synthesis was assessed by a DNA polymerase ␦ assay. A marked inhibition of both reactions was found. Unexpectedly, PARP-1 activity also decreased in the presence of p21 waf1/cip1. By pull-down experiments, we provided the first evidence for an association between PARP-1 and p21, which involves the C-terminal part of p21 protein. This association was further demonstrated to occur also in vivo in MNNG (N-methyl-N-nitro-N-nitrosoguanidine)-treated human fibroblasts. These observations suggest that PARP-1 and p21 could cooperate in regulating the functions of PCNA during DNA replication/repair.1 is a DNA-nick sensor protein that uses ␤-NAD ϩ as a substrate for transferring ADP-ribose moieties to itself and to nuclear acceptor proteins (1). PARP-1 modulates the structure and function of many proteins involved in DNA metabolism (2, 3), co-purifies with some members of the DNA synthesome (4 -6), and is a component of replication-competent complexes (7). It has been shown previously that PARP-1 co-immunoprecipitates with the proliferating cell nuclear antigen (PCNA) (4, 5), which is a pivotal protein in DNA replication, DNA repair, and cell cycle control. A number of proteins involved in DNA replication and repair interact with PCNA (reviewed in Refs. 8 -11). Most of the PCNA-interacting proteins have a QXX(h)XX(a)(a) box that specifically binds the interdomain connector loop (12). PARP-1 shows a putative PCNA-binding consensus sequence (QDLIK-MIF) at position 669 within the NAD-binding domain that is essential for the conversion of NAD into ADP-ribose and, consequently, for PARP-1 catalytic activity.In this work we sought to attain a greater understanding of the interaction between PARP-1 and PCNA. We have demonstrated that PARP-1 and PCNA co-immunoprecipitate both from the soluble and the DNA-bound fraction isolated from S-phase-synchronized HeLa cells. These results were supported by immunoprecipitation experiments with purified proteins. To investigate the effect of this association on the properties of each protein, we evaluated the conversion of NAD into ADP-ribose (PARP assay) as well as PCNA-dependent nucleotide incorporation (pol ␦ assay), and we found a marked inhibition of both reactions. Unexpectedly, an inhibitory effect on PARP-1 activity was al...

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Apoptosis-prone phenotype of human colon carcinoma cells with a high level amplification of the c-myc gene

Cited by 45 publications

References 49 publications

2-Methoxyestradiol: New perspectives in colon carcinoma treatment

2-Methoxyestradiol: New perspectives in colon carcinoma treatment

c-Myc antagonizes the effect of p53 on apoptosis and p21WAF1 transactivation in K562 leukemia cells

Human Proliferating Cell Nuclear Antigen, Poly(ADP-ribose) Polymerase-1, and p21 /

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