Abstract:
:Cells from patients with genomic instability syndromes have high predisposition to cancer. However, little is known about whether these mutant cells have high susceptibility to oncogenic transformation. We have tested the hypothesis that a defect in maintaining genome integrity is necessary but not sufficient alone for oncogenic transformation and needs to collaborate with other signals in order to produce full oncogenic transformation. Using genetically matched primary cells deficient for the Fanconi complementation group C gene (Fancc) and the ataxia telangiectasia mutated gene (Atm), we found that certain forms of oncogenic activation and cooperation require a combination of genomic instability with increased expression of nucleophosmin (NPM) to prevent oncogenic stress-induced apoptosis or senescence. Intriguingly, co-expression of c-Myc and NPM leads to a synergistic increase in the proliferation rate in Fancc-/- or Atm-/- cells. Analysis of p53 stabilization and activation by c-Myc demonstrates that over-expression of NPM significantly reduces the accumulation of the activated p53 but not the stability of p53. Moreover, NPM is shown to enhance transforming activity of co-expressed Myc and Ras in wild-type and, to a greater degree, in Fancc-/- or Atm-/- cells, suggesting a role in oncogenic cooperation. Finally, a partial knockdown of NPM is sufficient to cause massive apoptosis in Fancc-/- or Atm-/- cells co-expressing c-Myc and Ras while sparing untransformed cells. Our study demonstrates a novel mechanism of NPM tumorigenesis by establishing NPM as a crucial inhibitor of oncogene-induced apoptosis and senescence.
journal_name
Carcinogenesisjournal_title
Carcinogenesisauthors
Li J,Sejas DP,Burma S,Chen DJ,Pang Qdoi
10.1093/carcin/bgm025subject
Has Abstractpub_date
2007-06-01 00:00:00pages
1163-70issue
6eissn
0143-3334issn
1460-2180pii
bgm025journal_volume
28pub_type
杂志文章相关文献
CARCINOGENESIS文献大全abstract::The modulating effects of dietary feeding of two xanthophylls, astaxanthin (AX) and canthaxanthin (CX) during the postinitiation phase on colon carcinogenesis initiated with azoxymethane (AOM) were investigated in male F344 rats. Animals were initiated with AOM by weekly s.c. injections of 15 mg/kg body wt for 3 weeks...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/16.12.2957
更新日期:1995-12-01 00:00:00
abstract::p90 Ribosomal S6 kinase (RSK) 4 is a serine-threonine kinase that belongs to the p90RSK family. RSK4 has been proposed as a tumor suppressor gene, related with anti-invasive activity, inhibition of the RAS-mitogen-activated protein kinase (MAPK) pathway and induction of senescence. Despite the related findings, little...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/bgr003
更新日期:2011-04-01 00:00:00
abstract::In vitro activation of benzo[a]pyrene to protein-binding forms was investigated with the following two systems: (1) various fractions of human and rat blood had a potential of activating benzo[a]pyrene to forms binding to proteins in the presence of linoleic or arachidonic acid. Red blood cells activated much more ben...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/7.2.267
更新日期:1986-02-01 00:00:00
abstract::The role of bacteria in catalysing intragastric formation of N-nitrosothiazolidine-4-carboxylic acid and N-nitrosomorpholine was investigated in a rat model of omeprazole-induced achlorhydria. Omeprazole-treated rats gavaged with nitrosation-proficient bacteria were treated with nitrosamines and/or precursors and comp...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/12.3.435
更新日期:1991-03-01 00:00:00
abstract::The effects of retinol and retinoic acid on cytotoxicity and mutation expression at the hypoxanthine-guanine phosphoribosyl transferase (HGPRT) locus in Chinese hamster ovary (CHO) cells with or without exogenous metabolic activation were studied in the presence and absence of known chemical mutagens. Neither retinol ...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/9.7.1307
更新日期:1988-07-01 00:00:00
abstract::Naturally occurring antioxidants are extensively studied for their capacity to protect organisms and cells from damage induced by oxygen reactive species. In fact, oxidative stress is considered a cause of aging, degenerative disease and cancer. We have focused our attention on two agents, ascorbic acid and beta-carot...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/18.1.223
更新日期:1997-01-01 00:00:00
abstract::The purpose of this work was to study the relative activities and stabilities of phase-I and phase-II drug metabolizing enzymes in incubation mixtures used in vitro genotoxicity testing in order to optimize the conditions of the assay, increase sensitivity and eliminate false negative results. Cytochrome P-450, NADPH-...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/8.9.1179
更新日期:1987-09-01 00:00:00
abstract::It has been proposed that extremely low frequency magnetic fields may enhance tumorigenesis through a co-promotional mechanism. This hypothesis has been further tested using the two-stage model of mouse skin carcinogenesis, i.e. 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced promotion of skin carcinogenesis in mic...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/20.4.685
更新日期:1999-04-01 00:00:00
abstract::Vascular endothelial growth factor (VEGF) and hypoxia-inducible factor 1 (HIF-1) are important regulators of angiogenesis. HIF-1 is composed of HIF-1alpha and HIF-1beta subunits, and regulates VEGF expression at transcriptional level. In this study, we demonstrated that insulin induced H2O2 production and p70S6K1 acti...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/bgl085
更新日期:2007-01-01 00:00:00
abstract::Benzene, a ubiquitous environmental pollutant, is known to cause leukemia and aplastic anemia in humans and hematotoxicity and myelotoxicity in rodents. Toxicity is thought to be exerted through oxidative metabolites formed in the liver, primarily via pathways mediated by cytochrome P450 2E1 (CYP2E1). Phenol, hydroqui...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/20.8.1511
更新日期:1999-08-01 00:00:00
abstract::A decreased incidence of squamous cell carcinoma of the head and neck (SCCHN) associated with fruit and vegetable intake may act through chemopreventive compounds, which may be more available to persons homozygous for the deletion genotypes of the glutathione S-transferase (GST). We evaluated interactions between frui...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/bgh054
更新日期:2004-05-01 00:00:00
abstract::Mutations of the tumor suppressor gene p53 have been found in hepatocellular carcinomas (HCCs) from many countries where HCC is common, but p53 mutations detected by direct sequencing in HCCs from the United States (where HCC is uncommon) have been reported only rarely. p53 Exons 1 to 11 were analyzed by polymerase ch...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/17.10.2207
更新日期:1996-10-01 00:00:00
abstract::Chemotherapeutic agents have been the mainstay of cancer therapy for years. However, their effectiveness has been limited by toxicities they impart on normal cells. Staurosporine (ST) has been shown to arrest normal, but not breast cancer, cells in G1. Therefore, ST may become a chemoprotective agent, arresting normal...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/bgt186
更新日期:2013-10-01 00:00:00
abstract::Drug resistance is one of the main obstacles to the successful treatment of cancer. The availability of agents that are highly effective against drug-resistant cancer cells is therefore essential. The present study was performed to examine the anticancer effects of evodiamine, a major constituent of the Chinese herb E...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/bgi041
更新日期:2005-05-01 00:00:00
abstract::The present study was designed to evaluate the tolerance and cancer chemopreventive activity of triphenylselenonium chloride in female Sprague-Dawley rats. No information is available in the literature on the anticarcinogenic efficacy of a lipophilic cationic selenium compound as exemplified by the triphenylselenonium...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/15.12.2879
更新日期:1994-12-01 00:00:00
abstract::Mutant RAS (RAS(V12)) is known to transform most immortal cells but to induce premature senescence in primary cells. RAS(V12)-induced senescence in murine cells depends on the induction of the ARF/p53 and the retinoblastoma (Rb) family tumor suppressor pathways. We and others have shown previously that oncogene-induce...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/bgp296
更新日期:2010-02-01 00:00:00
abstract::A topical application of a chalcone derivative, 4,2',4'-trihydroxychalcone (isoliquiritigenin) inhibited epidermal ornithine decarboxylase (ODC) induction and ear edema formation, i.e. inflammation, caused by a topical application of 12-O-tetradecanoylphorbol-13-acetate (TPA) in CD-1 mice. In addition, isoliquiritigen...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/12.2.317
更新日期:1991-02-01 00:00:00
abstract::Oxidized DNA base lesions, such as thymine glycol (Tg) and 8-hydroxyguanine, are often toxic and mutagenic and have been implicated in carcinogenesis. To clarify whether NEIL1 protein, which exhibits excision repair activity towards such base lesions, is involved in gastric carcinogenesis, we examined 71 primary gastr...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/bgh267
更新日期:2004-12-01 00:00:00
abstract::Reflux of gastroduodenal contents and consequent inflammatory responses are associated with the development of Barrett's oesophagus (BO) and the promotion of oesophageal adenocarcinoma (OAC). Deregulation of inflammatory processes is a hallmark of oesophageal cancer. In this study, we aimed to investigate (i) the tran...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/bgq036
更新日期:2010-05-01 00:00:00
abstract::Telomeres are critical in maintaining chromosome and genomic stability. Arsenic, a human carcinogen as well as an anticancer agent, is known for its clastogenicity. To better understand molecular mechanisms of arsenic actions, we investigated arsenite effects on telomere and telomerase and determined cell growth and a...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/bgg141
更新日期:2003-11-01 00:00:00
abstract::Measurements were made of the effects of phenolic compounds, some of which are present in the human diet, on the nitrosation of proline by nitrite to give N-nitrosoproline (NPRO). In vitro, resorcinol, catechin, p-nitrosophenol and phenol were catalysts and chlorogenic acid an inhibitor; guaiacol showed a marginal cat...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/3.9.1045
更新日期:1982-01-01 00:00:00
abstract::Using conventional alkaline sucrose sedimentation analysis, we have compared the initial yield and subsequent enzymatic repair of DNA damage induced in cultured human [normal (GM38 and GM43) and xeroderma pigmentosum (XP12BE)] fibroblasts by the monofunctional alkylating agent methylmethanesulfonate (MMS). Exposure of...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/9.12.2257
更新日期:1988-12-01 00:00:00
abstract::To study the roles of DNA polymerases alpha and beta during replication and repair of damaged DNA, use was made of the fact that during chronic treatment with carcinogens, replication and repair do not necessarily follow the same time sequence. Early cell damage and restorative hyperplasia cause a transient wave of DN...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/2.1.61
更新日期:1981-01-01 00:00:00
abstract::Oreochromis mossambicus, commonly known as tilapia, is a freshwater teleost with a wide tolerance to environmental conditions. Multiple focal lesions in the liver were observed 2 months after cessation of a one-month long treatment with 100 p.p.m. diethylnitrosamine. Cells were small and compact and arranged in sheets...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/10.3.493
更新日期:1989-03-01 00:00:00
abstract::Induction of glutathione S-transferase (GST) enzymes can increase detoxification of carcinogens and reduce carcinogen-induced mutagenesis and tumorigenesis. To determine if the anticarcinogen ellagic acid induces cellular enzymes which detoxify carcinogens, we examined the effect of ellagic acid on the expression of g...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/16.3.665
更新日期:1995-03-01 00:00:00
abstract::The reason for different phosphorylation of topoisomerase I in two sublines of L5178Y murine lymphoma (LY cells) was investigated. Camptothecin-resistant LY-S cells show increased poly(ADP-ribose) level and lowered topoisomerase I phosphorylation compared to camptothecin-sensitive LY-R cells. In this study diminished ...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/17.3.383
更新日期:1996-03-01 00:00:00
abstract::Cancer-associated fibroblasts (CAFs) have been considered to play an important role for tumor progression of cancer. Solid tumors contain heterogeneous distribution of oxygen in their microenvironments. This study investigated the growth signaling of gastric cancer (GC) cells in focus on the interaction with CAFs and ...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/bgv134
更新日期:2015-12-01 00:00:00
abstract::Progress in prostate cancer research has been hindered by the lack of well characterized, immortalized, human prostatic epithelial cell lines that express markers of normal prostatic epithelial cells and mimic normal growth and differentiation responses to androgens. The objectives of this study were to: (i) establish...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/17.8.1641
更新日期:1996-08-01 00:00:00
abstract::An enhancement of the cellular cAMP level has been shown to protect against phorbol ester-induced inhibition of gap junctional intercellular communication (GJIC) and induction of morphological transformation in Syrian hamster embryo (SHE) cells. Cholera toxin, forskolin, 3-isobutyl-1-methylxanthine (IBMX) and theophyl...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/13.10.1803
更新日期:1992-10-01 00:00:00
abstract::The metastasis suppressor, N-myc downstream-regulated gene-1 (NDRG1), plays multifaceted roles in inhibiting oncogenic signaling and can suppress the epithelial mesenchymal transition (EMT), a key step in metastasis. In this investigation, NDRG1 inhibited the oncogenic effects of transforming growth factor-β (TGF-β) i...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/bgy178
更新日期:2019-07-06 00:00:00