Abstract:
:The Notch pathway plays a key role in the development and is increasingly recognized for its importance in cancer. We demonstrated previously the overexpression of Notch-1 and its ligands in gliomas and showed that their knockdown inhibits glioma cell proliferation and survival. To elucidate the mechanisms downstream of Notch-1 in glioma cells, we performed microarray profiling of glioma cells transfected with Notch-1 small interfering RNA. Notable among downregulated transcripts was the epidermal growth factor receptor (EGFR), known to be overexpressed or amplified in gliomas and prominent in other cancers as well. Further studies confirmed that Notch-1 inhibition decreased EGFR messenger RNA (mRNA) and EGFR protein in glioma and other cell lines. Transfection with Notch-1 increased EGFR expression. Additionally, we found a significant correlation in levels of EGFR and Notch-1 mRNA in primary high-grade human gliomas. Subsequent experiments showed that p53, an activator of the EGFR promoter, is regulated by Notch-1. Experiments with p53-positive and -null cell lines confirmed that p53 partially mediates the effects of Notch-1 on EGFR expression. These results show for the first time that Notch-1 upregulates EGFR expression and also demonstrate Notch-1 regulation of p53 in gliomas. These observations have significant implications for understanding the mechanisms of Notch in cancer and development.
journal_name
Carcinogenesisjournal_title
Carcinogenesisauthors
Purow BW,Sundaresan TK,Burdick MJ,Kefas BA,Comeau LD,Hawkinson MP,Su Q,Kotliarov Y,Lee J,Zhang W,Fine HAdoi
10.1093/carcin/bgn079subject
Has Abstractpub_date
2008-05-01 00:00:00pages
918-25issue
5eissn
0143-3334issn
1460-2180pii
bgn079journal_volume
29pub_type
杂志文章相关文献
CARCINOGENESIS文献大全abstract::The effects of exposure to benzo[a]pyrene (BAP) and formaldehyde (HCHO), alone and combined, on the induction of carcinogenesis in rat tracheal implants was determined as the number of growth-altered cell populations (tumor-initiation sites, TIS) per trachea. While exposure twice-weekly for 4.5 months to 0.2% HCHO sol...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/8.12.1951
更新日期:1987-12-01 00:00:00
abstract::The caspase proteins are essential for the regulation of normal B cell development and regulation of apoptosis. We investigated five single nucleotide polymorphisms in four key caspase genes, CASP3 [Ex8-280C>A (rs6948) and Ex8+567T>C (rs1049216)], CASP8 Ex14-271A>T (rs13113), CASP9 Ex5+32G>A (rs1052576) and CASP10 Ex3...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/bgl196
更新日期:2007-04-01 00:00:00
abstract::Continuous dietary administration of the hepatocarcinogen 2-acetylaminofluorene (AAF) to rats produces a gradual increase in hepatic DNA adducts until a plateau is reached after approximately 2 weeks. The rate of DNA adduct formation remains constant through 1 month of AAF feeding, while adduct removal profiles are bi...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/11.8.1343
更新日期:1990-08-01 00:00:00
abstract::Loss of gap junctional intercellular communication (GJIC) is a characteristic of cancer cells. Since a coordinated interaction of epithelial tumor cells with stromal cells is a prerequisite for tumor invasion and metastasis, the present study was designed to test the hypothesis that skin-derived tumor cells may modula...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/bgg153
更新日期:2003-11-01 00:00:00
abstract::Occupational exposure to hydrocarbon solvents has been found to be associated with an increased risk of exocrine pancreatic cancer (EPC), the human tumor with the highest prevalence of K-ras mutations. Ras genes are critical DNA targets for chemical carcinogens. We analysed the relationship between past occupational e...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/23.1.101
更新日期:2002-01-01 00:00:00
abstract::A growing body of evidence from human and animal cancer cytogenetics studies indicates that aneuploidy is an important chromosome change in carcinogenesis. To understand the role of this genetic phenomenon during the first steps of an experimental cancer model, molecular and cellular techniques were combined. A sequen...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/16.8.1825
更新日期:1995-08-01 00:00:00
abstract::Modification of 3,2'-dimethyl-4-aminobiphenyl (DMAB) multi-organ carcinogenesis by simultaneous treatment with butylated hydroxyanisole (BHA) or butylated hydroxytoluene (BHT) was studied using young and old male F344 rats. Animals, 4 or 54 weeks old, were given DMAB (s.c. injection of 50 mg/kg body wt once a week for...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/12.7.1335
更新日期:1991-07-01 00:00:00
abstract::Dose response studies regarding the cancer initiating potential of fumonisin B1 (FB1) were conducted as a function of time. Feeding studies over 21 days indicated that FB1 induced a feed refusal effect in rats at dietary levels of 250, 500 and 750 mg FB1/kg diet. This effect was overcome after 14 days and the feed int...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/15.2.209
更新日期:1994-02-01 00:00:00
abstract::N2-ethylidene-2'-deoxyguanosine (N2-ethylidene-dG) is a major DNA adduct induced by acetaldehyde. Although it is unstable in the nucleoside form, it is relatively stable when present in DNA. In this study, we analyzed three acetaldehyde-derived DNA adducts, N2-ethylidene-dG, N2-ethyl-2'-deoxyguanosine (N2-Et-dG) and a...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/bgm057
更新日期:2007-11-01 00:00:00
abstract::Covalent binding of [7-3H]styrene (S) to DNA in vivo was measured and evaluated in a quantitative manner in order to investigate whether DNA adduct formation could form a mechanistic basis for tumor induction in a carcinogenicity bioassay. [7-3H]S was administered by inhalation in a closed chamber to male and female C...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/14.3.355
更新日期:1993-03-01 00:00:00
abstract::A simple method for detection of DNA single-strand breaks (DNA-SSB) in cultured cells is described, based on filtration of alkaline-lysed cells through microfilters. After exposure to potentially DNA damaging agents, the cells are transferred to 0.8 micron cellulose acetate filters mounted in microfilter devices where...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/15.1.137
更新日期:1994-01-01 00:00:00
abstract::Several studies have shown that hexavalent chromium [Cr(VI)] induces apoptosis in a variety of in vitro test systems. We instilled intra-tracheally either saline or sodium dichromate (0.25 mg/kg body weight), for three consecutive days, to Sprague-Dawley rats. TUNEL analyses showed a marked increase of the apoptotic i...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/23.4.587
更新日期:2002-04-01 00:00:00
abstract::The oxidative metabolites of estrogen have been proposed to play an important role in the development of some human cancers. The two major pathways of estrogen metabolism, to the carcinogenic 4-hydroxyestradiol (4-OHE2) and to the non-carcinogenic 2-hydroxyestradiol (2-OHE2), are mediated by cytochromes P450 CYP1B1 an...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/23.10.1625
更新日期:2002-10-01 00:00:00
abstract::Phosphoinositide-specific phospholipase Cgamma (PLCgamma) is a key regulatory enzyme that binds to the phosphoryl-tyrosine residues in the cytoplasmic domain of certain activated receptors and catalyses the hydrolysis of phosphatidylinositol 4,5-bisphosphate [PtdIns(4,5)P2] forming IP3 and diacylglycerol (DAG) in resp...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/19.1.177
更新日期:1998-01-01 00:00:00
abstract::Gene-environment interactions play an important role in folate metabolism, with a potential impact on human health. Deficiencies in the uptake of key micronutrients and variant genotypes can affect the folic acid cycle, modulating methyl group transfer in key processes and leading to increased cancer risk and Down syn...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/bgg064
更新日期:2003-06-01 00:00:00
abstract::Patients with familial adenomatous polyposis (FAP) have a high risk of developing duodenal adenomas and carcinomas. The distribution of these neoplasms resembles mucosal exposure to bile, suggesting that bile may play a role in adenoma development. Our previous results, using DNA adducts detected by 32P-postlabelling ...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/14.6.1107
更新日期:1993-06-01 00:00:00
abstract::O-Methylation of catecholestrogens catalyzed by catechol-O-methyltransferase provides a major route for the rapid metabolic clearance of these steroids. However, the metabolic clearance rate of 4-hydroxyestradiol (4-OH-E2) is considerably lower than that of 2-hydroxyestradiol, although 2- and 4-hydroxycatecholestrogen...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/11.3.459
更新日期:1990-03-01 00:00:00
abstract::Inbred strains of mice with differential response to known tumor promoters were compared with respect to their susceptibility to modulation of hepatic antioxidant enzymes by long-term treatment with high fat diet (HF) and phenobarbital (PB). Mice of the C57BL/6J (C57), C3H/HeOuJ (C3H) and DBA/2J (DBA) strains were fed...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/14.6.1225
更新日期:1993-06-01 00:00:00
abstract::To elucidate the mechanism of metabolic activation of 3'-methyl-N,N-dimethyl-4-aminoazobenzene (3'-Me-DAB), the mutagenicity of its metabolites and some related azo compounds towards Salmonella typhimurium TA-98 and TA-100 was investigated. Mutagenicity of the metabolites, either N-demethylated or oxidized at the 3'-m...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/1.2.121
更新日期:1980-02-01 00:00:00
abstract::We investigated, in a cloned hamster tracheal epithelial cell line HTE-B, the effects of inhibitors of DNA topoisomerase, novobiocin and nalidixic acid; of DNA polymerase, 1-beta-arabinofuranosylcytosine (ara-C) and 2',3'-dideoxythymidine; of ribonucleotide reductase, hydroxyurea; and of poly(ADP-ribose)synthetase, 3-...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/5.2.187
更新日期:1984-02-01 00:00:00
abstract::We have previously demonstrated that betel quid containing safrole induced DNA adducts are highly associated with the development of oral squamous cell carcinoma (OSCC) in Taiwan. Sulfotransferase (SULT) is essential for the formation of these adducts. To elucidate the effects of SULT1A1 haplotypes on OSCC susceptibil...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/bgn283
更新日期:2009-02-01 00:00:00
abstract::Colorectal cancer (CRC) is the third most common cancer worldwide. Chronic inflammation appears to enhance the risk of CRC. Emerging evidence has suggested that epigenetic mechanisms play an important role in CRC. Aspirin [acetylsalicylic acid (ASA)] has been shown to prevent CRC; however, the epigenetic mechanisms of...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/bgw042
更新日期:2016-06-01 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::No previous study has examined the association between mitochondrial DNA copy number (mtCN) and skin cancer risk prospectively. We examined the associations between peripheral blood leukocytes mtCN level and the risks of skin cancers in a case-control study nested within the Nurses' Health Study of non-Hispanic White ...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/bgw072
更新日期:2016-09-01 00:00:00
abstract::The mutagenicity of the lipid peroxidation product, malondialdehyde (MDA), was measured in the lacZ alpha forward mutation assay using a recombinant M13 phage, M13MB102. Single-stranded M13MB102 DNA was reacted with MDA at neutral pH and the modified DNA was transformed into strains of Escherichia coli induced for the...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/16.1.93
更新日期:1995-01-01 00:00:00
abstract::Lack of functional telomeres can cause chromosomal aberrations. This type of genetic instability may promote tumorigenesis. We have investigated the association between mean telomere length in buccal cells (assessed with quantitative real-time PCR) and bladder cancer risk in a case-control study. Patients with bladder...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/bgi063
更新日期:2005-07-01 00:00:00
abstract::The liver-derived human cell line, Hep G2, has high benzo[a]pyrene-metabolizing activity and converts benzo[a]pyrene to intermediates that are mutagenic and that bind to DNA. This cell line will be useful for studying metabolic activation of polycyclic aromatic hydrocarbons and other xenobiotics by human tissue and as...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/1.10.871
更新日期:1980-01-01 00:00:00
abstract::Human papillomavirus (HPV) type 16 infection is an etiologic factor in a subset of head and neck squamous cell carcinomas (HNSCC). It is unknown if host genetic susceptibility modifies the HPV16-HNSCC association. DNA samples collected as part of a Boston area case-control study of HNSCC were genotyped for single-nucl...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/bgp076
更新日期:2009-06-01 00:00:00
abstract::The methylation status of the rat gamma-glutamyl transpeptidase (GGT) gene was investigated during liver development and hepatocarcinogenesis. The analysis with the restriction enzymes MspI/HpaII revealed that, during ontogeny, there is a progressive methylation of the GGT gene that coincides with a progressive decrea...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/12.6.1035
更新日期:1991-06-01 00:00:00
abstract::Estrogen production and metabolism play critical roles in the development and pathogenesis of endometrial carcinoma. Cytochrome P450 1B1 (CYP1B1) and catechol-O-methyltransferase (COMT) are two key enzymes in the estrogen metabolism pathway that result in the hydroxylation and conjugation of estradiol, respectively. W...
journal_title:Carcinogenesis
pub_type: 杂志文章,多中心研究
doi:10.1093/carcin/bgh039
更新日期:2004-04-01 00:00:00