Abstract:
:Neuroblastic tumors (NTs) include the neuroblastomas, ganglioneuroblastomas and ganglioneuromas. We have reported previously that the calcium-sensing receptor is expressed in differentiated, favorable NTs but almost undetectable in unfavorable neuroblastomas. We have now detected hypermethylation of a particular region within the CpG island encompassing the CaSR gene promoter 2 in neuroblastoma cell lines and 25% primary neuroblastomas. Hypermethylation of this region was associated with reduced CaSR messenger RNA expression and several predictors of poor outcome in neuroblastomas, including MYCN amplification. Treatment with 5'aza-2-deoxycitidine and/or trichostatin A restored CaSR expression in MYCN-amplified cell lines. Following 5'aza-2-deoxycitidine exposure, decreased percentages of methylated CpG sites were observed at the above-mentioned region. By interphase fluorescence in situ hybridization, variable percentages of nuclei with monosomy of chromosome 3, where the human CaSR gene resides, were observed in more than 90% of primary NTs of all subgroups. Nuclei harboring this alteration were heterogeneously distributed among tumor cells. Ectopic overexpression of the calcium-sensing receptor in two MYCN-amplified neuroblastoma cell lines in which this gene is silenced by promoter hypermethylation significantly reduced their in vitro proliferation rates and almost abolished their capacity to generate xenografts in immunocompromised mice. Finally, upon acute exposure to calcium, the primary activator of this receptor, calcium-sensing receptor-overexpressing neuroblastoma cells underwent apoptosis, a process dependent on sustained activation of ERK1/2. These data would support the hypothesis that epigenetic silencing of the CaSR gene is neither an in vitro artefact in neuroblastoma cell lines nor an irrelevant, secondary event in primary NTs, but a significant mechanism for neuroblastoma survival.
journal_name
Carcinogenesisjournal_title
Carcinogenesisauthors
Casalà C,Gil-Guiñón E,Ordóñez JL,Miguel-Queralt S,Rodríguez E,Galván P,Lavarino C,Munell F,de Alava E,Mora J,de Torres Cdoi
10.1093/carcin/bgs338subject
Has Abstractpub_date
2013-02-01 00:00:00pages
268-76issue
2eissn
0143-3334issn
1460-2180pii
bgs338journal_volume
34pub_type
杂志文章相关文献
CARCINOGENESIS文献大全abstract::Four monoclonal antibodies, PhIP-1, -2, -3 and -4, have been produced that bind to PhIP (2-amino-1-methyl-6-phenyl-imidazo[4,5-b]pyridine), a mutagenic aromatic amine produced in meat by cooking. The immunogen was an analog of PhIP conjugated to a carrier protein through the 2-amino group of PhIP, leaving the pyridine...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/10.12.2215
更新日期:1989-12-01 00:00:00
abstract::The hepatitis B virus X protein (HBx) has pleiotropic biological effects, which underlies its potential role in cell transformation. However, its involvement in hepatic fibrosis remains unclear. In this study, we wanted to clarify, in vivo, the role of HBx protein in the development of liver fibrosis. Mice transgenic ...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/bgz109
更新日期:2020-05-14 00:00:00
abstract::The mechanism of inactivation of the O6-methylguanine-DNA methyltransferase (MGMT), responsible for repair of mutagenic and cytotoxic O6-alkylguanine, in Mex- tumor cells, is not completely understood. We have examined the role of CpG methylation in the human MGMT promoter in a luciferase (luc) reporter plasmid and as...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/bgg086
更新日期:2003-08-01 00:00:00
abstract::Whole-body autoradiography of [3H]aflatoxin B1 ([3H]AFB1) in lamb showed a localization of bound labelling, in addition to the liver, in the nasal olfactory and respiratory mucosa, in the mucosa of the nasopharynx, pharynx, oesophagus, larynx, trachea, bronchi and bronchioles and in the palpebral and bulbar conjunctiv...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/15.5.947
更新日期:1994-05-01 00:00:00
abstract::Extensive tumorigenicity studies in rodents revealed that dibenzo[a,l]pyrene (DB[a,l]P) is the most potent carcinogen among all polycyclic aromatic hydrocarbons (PAHs) tested so far. The structure of the genotoxic metabolite(s) responsible for this exceptional carcinogenicity is unknown. The fjord-region syn- and anti...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/15.11.2507
更新日期:1994-11-01 00:00:00
abstract::We have compared liver, kidney and colon DNA damage, as single strand breaks, in mice with different strain-dependent susceptibility to the colon-specific carcinogen 1,2-dimethylhydrazine (DMH). The mouse strains studied were: AKR/J, DBA2 totally resistant; CD1, C57BL/6N moderately susceptible; SWR/J very susceptible ...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/9.8.1347
更新日期:1988-08-01 00:00:00
abstract::Lung tumors were induced in A/J mice by the tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and the related compounds acetoxymethylmethylnitrosamine (AMMN) and 4-acetoxymethylnitrosamino)-1-(3-pyridyl)-1-butanone (NNKOAc). NNK both methylates and pyridyloxobutylates DNA while AMMN and...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/14.11.2419
更新日期:1993-11-01 00:00:00
abstract::1,3-Dimethyl-3-phenyl-1-nitrosourea (DMPNU) shows no spontaneous decomposition in aqueous buffered solution (pH 7.0) at 37 degrees C over a measuring period of 10 days, but it is directly genotoxic in all assays applied. This compound induces base substitutions in Salmonella typhimurium (especially in the plasmid harb...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/4.4.409
更新日期:1983-01-01 00:00:00
abstract::An iron chelate, ferric nitrilotriacetate (Fe-NTA), induces renal proximal tubular damage, a consequence of iron-catalysed Fenton-like reactions, that finally leads to a high incidence of renal cell carcinoma (RCC) in rodents. Glutathione S-transferase (GST) is a family of enzymes that play an important role in detoxi...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/19.5.897
更新日期:1998-05-01 00:00:00
abstract::High intake of red meat is associated with an increased risk of colon cancer. It has been suggested that fat from red meat is responsible, because high fat intake increases the concentration of cytotoxic lipids in the colon. Experimental studies have not unequivocally supported such a role for fat, however. Recently, ...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/21.10.1909
更新日期:2000-10-01 00:00:00
abstract::Strains of laboratory mice vary markedly in their susceptibility to two-stage skin carcinogenesis using 7,12-dimethylbenz[a]anthracene (DMBA) as the initiating carcinogen and croton oil as promoter. This study has been undertaken in order to clarify the basis of the strain differences. LACA mice were used as the susce...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/3.1.99
更新日期:1982-01-01 00:00:00
abstract::A plant polysaccharide, Aloe gel extract, was reported to have an inhibitory effect on benzo[a]pyrene (B[a]P)-DNA adduct formation in vitro and in vivo. Hence, chemopreventive effects of plant polysaccharides [Aloe barbadensis Miller (APS), Lentinus edodes (LPS), Ganoderma lucidum (GPS) and Coriolus versicolor (CPS)] ...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/20.8.1637
更新日期:1999-08-01 00:00:00
abstract::The carcinogenicities of 1-nitropyrene (1-NP), 4-nitropyrene (4-NP), 1,3-dinitropyrene (1,3-DNP), 1,6-dinitropyrene (1,6-DNP), 1,8-dinitropyrene (1,8-DNP), 3-hydroxy-1-nitropyrene (3-OH-1-NP) and a mixture of 6- and 8-hydroxy-1-nitropyrene (6/8-OH-1-NP) were investigated in newborn female rats. Newborn female CD rats ...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/16.12.3027
更新日期:1995-12-01 00:00:00
abstract::In this communication, we investigate the preventive effect of a flavonoid antioxidant, silymarin, on free radical-generating skin tumor promoting agent benzoyl peroxide (BPO)-induced tumor promotion, oxidative stress and inflammatory responses in SENCAR mouse skin. Topical application of silymarin at a dose of 6 mg p...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/21.4.811
更新日期:2000-04-01 00:00:00
abstract::DNA strand breage in response to damage produced by UV (254 nm) radiation was characterized after permeabilization of diploid normal and xeroderma pigmentosum variant fibroblasts. The breakage reaction required ATP, Mg2+ and sucrose for maximal activity and was inhibited by 150 mM Na+ or K+ and 1 mM N-ethylmaleimide. ...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/11.1.15
更新日期:1990-01-01 00:00:00
abstract::The HSP70 family of heat shock proteins consists of molecular chaperones of approximately 70kDa in size that serve critical roles in protein homeostasis. These adenosine triphosphatases unfold misfolded or denatured proteins and can keep these proteins in an unfolded, folding-competent state. They also protect nascent...
journal_title:Carcinogenesis
pub_type: 杂志文章,评审
doi:10.1093/carcin/bgt111
更新日期:2013-06-01 00:00:00
abstract::Elevated Bcl-xL expression in cancer cells contributes to doxorubicin (DOX) resistance, leading to failure in chemotherapy. In addition, the clinical use of high-dose doxorubicin (DOX) in cancer therapy has been limited by issues with cardiotoxicity and hepatotoxicity. Here, we show that co-treatment with pyrrolidine ...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/bgy003
更新日期:2018-03-08 00:00:00
abstract::Serum-free cultures of normal human buccal epithelial cells were transfected with a plasmid containing the SV40 T-antigen (SV40T) gene. Two major lines developed that showed extended lifespans (between 30 and 40 weeks) as compared with the controls (approximately 6 weeks). Continued growth through one or two crises ge...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/16.10.2515
更新日期:1995-10-01 00:00:00
abstract::The inability of cells in culture to grow in medium where methionine is replaced by its metabolic precursor, homocysteine, has been linked to neoplastic transformation and termed 'methionine dependence' or 'methionine auxotrophy'. The present investigation was undertaken to establish the influence of intracellular glu...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/12.2.241
更新日期:1991-02-01 00:00:00
abstract::The genes that are involved in estrogen biosynthesis, cellular binding and metabolism may contribute to breast cancer susceptibility. We examined the effect of the CYP17 promoter T --> C polymorphism and its interactions with the reproductive history, exogenous hormone use and selected lifestyle risk factors on breast...
journal_title:Carcinogenesis
pub_type: 杂志文章,多中心研究
doi:10.1093/carcin/bgn042
更新日期:2008-04-01 00:00:00
abstract::Wildtype 10T1/2 cells and 42 clonally derived morphologically transformed 10T1/2 cell lines were evaluated for expression of p53 mRNA and protein. Wildtype 10T1/2 cells expressed detectable levels of p53 mRNA and multiple immunologically distinct forms of the p53 protein, including both PAb240- and PAb246-reactive con...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/15.2.145
更新日期:1994-02-01 00:00:00
abstract::The nasal passages are a common portal of entry and are a prime site for toxicant-induced pathology. Sustained increases in regenerative cell proliferation can be a significant driving force in chemical carcinogenesis. The atmosphere in Mexico City contains a complex mixture of air pollutants and its residents are exp...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/20.3.383
更新日期:1999-03-01 00:00:00
abstract::2-Nitrofluorene (NF) is a potent genotoxic substance found in environments where incomplete combustion takes place. NF is a mutagen and a carcinogen in animal models. NF or 7,12-dimethylbenz[a]anthracene (DMBA) was administered once topically to female SENCAR mice followed by promotion by 12-O-tetradecanoylphorbol-13-...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/14.8.1723
更新日期:1993-08-01 00:00:00
abstract::Chronic oral administration of the carcinogenic aminoazo dye N-methyl-4-aminoazobenzene (MAB) to rats is known to result in the induction of liver tumors. In order to assess the role of carcinogen-DNA adduct formation in MAB hepatocarcinogenesis, male rats were fed 0.06% [3'-3H]MAB in the diet for 1, 3 or 5 weeks. Gro...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/8.4.577
更新日期:1987-04-01 00:00:00
abstract::Pancreatic cancer has remained refractory to treatment. In large part, this results from the lack of an animal model that mimics pancreatic cancer in man. We describe a novel experimental model of pancreatic cancer that shares the genetic background, histologic features and natural history of human mixed acinar-ductal...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/bgx119
更新日期:2018-02-09 00:00:00
abstract::The possible roles of cytochrome P450 (P450) enzymes in the metabolic activation of N-nitrosodimethylamine (NDMA) and N-nitrosodiethylamine (NDEA) by rat liver microsomes have been examined in a system containing the bacterial tester strain Salmonella typhimurium NM2009, a newly developed strain showing high O-acetylt...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/13.6.979
更新日期:1992-06-01 00:00:00
abstract::Cyproterone acetate (CPA) is a synthetic steroid which is used in oral contraceptive and anti-androgen formulations. It has previously been classified as a tumor promoter in rat liver. Recent studies have shown that CPA induces DNA repair synthesis in isolated hepatocytes, and this implies that CPA is genotoxic. We st...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/14.6.1229
更新日期:1993-06-01 00:00:00
abstract::Nutritional deficiencies or imbalances are suspected contributory factors to several types of human cancers, and perhaps other human diseases related to long-term metabolic derangements. In order to study these more effectively in laboratory animals, it is suggested that the laboratory diets more closely mimic the nut...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/8.7.871
更新日期:1987-07-01 00:00:00
abstract::Naturally occurring allyl isothiocyanate (AITC) was recently shown to be selectively delivered to bladder cancer tissue via urinary excretion and to inhibit bladder cancer growth and muscle invasion in an animal model. AITC is excreted in urine mainly as N-acetyl-S-(N-allylthiocarbamoyl)cysteine, more commonly known a...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/bgr283
更新日期:2012-02-01 00:00:00
abstract::The aim of the present study was to investigate the impact of four different lactobacillus (LB) strains, namely Lactobacillus bulgaricus 291, Streptococcus thermophilus F4, S.thermophilus V3 and Bifidobacterium longum BB536, which are used for the production of yogurt, on the DNA-damaging effects of heterocyclic aroma...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/bgg167
更新日期:2003-12-01 00:00:00