Abstract:
:Insulin-like growth factor-binding protein (IGFBP)-3 is overexpressed frequently in esophageal squamous cell carcinoma. Yet, the role of IGFBP3 in esophageal tumor biology remains to be elucidated. We find that IGFBP3 facilitates transforming growth factor (TGF)-beta1-mediated epithelial-to-mesenchymal transition (EMT) in transformed human esophageal epithelial cells, EPC2-hTERT-EGFR-p53(R175H). In organotypic 3D culture, a form of human tissue engineering, laser-capture microdissection revealed concurrent upregulation of TGF-beta target genes, IGFBP3 and EMT-related genes in the cells invading into the stromal compartment. IGFBP3 enhanced TGF-beta1-mediated EMT as well as transcription factors essential in EMT by allowing persistent SMAD2 and SMAD3 phosphorylation. TGF-beta1-mediated EMT and cell invasion were enhanced by ectopically expressed IGFBP3 and suppressed by RNA interference directed against IGFBP3. The IGFBP3 knockdown effect was rescued by IGFBP3(I56G/L80G/L81G), a mutant IGFBP3 lacking an insulin-like growth factor (IGF)-binding capacity. Thus, IGFBP3 can regulate TGF-beta1-mediated EMT and cell invasion in an IGF or insulin-like growth factor 1 receptor-independent manner. IGFBP3(I56G/L80G/L81G) also promoted EMT in vivo in a Ras-transformed human esophageal cell line T-TeRas upon xenograft transplantation in nude mice. In aggregate, IGFBP3 may have a novel IGF-binding independent biological function in regulation of TGF-beta1-mediated EMT and cell invasion.
journal_name
Carcinogenesisjournal_title
Carcinogenesisauthors
Natsuizaka M,Ohashi S,Wong GS,Ahmadi A,Kalman RA,Budo D,Klein-Szanto AJ,Herlyn M,Diehl JA,Nakagawa Hdoi
10.1093/carcin/bgq108subject
Has Abstractpub_date
2010-08-01 00:00:00pages
1344-53issue
8eissn
0143-3334issn
1460-2180pii
bgq108journal_volume
31pub_type
杂志文章相关文献
CARCINOGENESIS文献大全abstract::In hepatocellular carcinoma (HCC), a subset of cells defined by high CD44 and CD133 expression has been reported to possess cancer stem-like cell (CSC) characteristics and to be associated with a poor prognosis. Since the approval of the multi-kinase inhibitor, lenvatinib, for patients with unresectable HCC, two such ...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/bgaa049
更新日期:2020-05-25 00:00:00
abstract::The apoptotic response to DNA damage appears to be an innate biological mechanism for protection against tumourigenesis. It is possible that agents that protect against colorectal cancer act by enhancing the apoptotic deletion of cells suffering DNA damage, with consequent removal of those with tumourigenic mutations....
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/23.7.1131
更新日期:2002-07-01 00:00:00
abstract::The aim of this study has been to define cytotoxic mechanisms that may cause clonal expansion in the liver of pre-carcinogenic cells. An in vitro model, which has been described previously, was used. Hepatocytes were isolated from carcinogen-treated rats and a high proportion of the cells were gamma-glutamyltranspepti...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/11.1.69
更新日期:1990-01-01 00:00:00
abstract::Recent studies have proposed that exposure to ultraviolet radiation (UVR) protects against development of some internal cancers including that in prostate. This effect may be mediated by UVR-induced cutaneous synthesis of vitamin D. It is also proposed that ability to pigment in response to UVR will influence suscepti...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/bgg021
更新日期:2003-04-01 00:00:00
abstract::The promoting action of hexachlorocyclohexane (HCH) was evaluated in female Wistar rats by counting the gamma-glutamyltranspeptidase-positive foci which appeared in the liver after diethylnitrosamine (DENA) initiation. Liver tumor promotion by HCH was further confirmed in a long-term tumorigenicity study after DENA pr...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/5.4.479
更新日期:1984-04-01 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::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 regio...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/bgs338
更新日期:2013-02-01 00:00:00
abstract::In two separate in vivo studies, ethionine was evaluated for carcinogenic activity in mice. In the first study, DL-ethionine was fed in a chow diet at 0 (controls), 0.1 (low dose, LD) and 0.25% (high dose, HD) concentrations to the following groups of mice (30 animals/group): Swiss Webster CD-1 females, BALB/c males, ...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/7.7.1143
更新日期:1986-07-01 00:00:00
abstract::The urinary excretion of dimethylnitrosamine (DMN) was studied in male Sprague-Dawley rats. Animals were given DMN (3, 5, 10, 20, 30 and 50 mg/kg body weight, i.p.) or [3H]DMN (0.1, 1 and 3 mg; 8.7, 1.5 and 0.28 mCi/kg body weight, respectively, i.p.) diluted with sterile 0.9% NaCl. Urine was collected for 24 h after ...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/2.7.609
更新日期:1981-01-01 00:00:00
abstract::Human Papillomavirus (HPV) positive oropharyngeal squamous cell carcinoma (HPV+OPSCC) is increasing in prevalence in the United States, as are cases of patients with multiple HPV+OPSCCs (mHPV+OPSCC). mHPV+OPSCCs present a unique opportunity to examine HPV+OPSCC mutation acquisition and evolution. We performed sequenci...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/bgaa111
更新日期:2020-10-19 00:00:00
abstract::We present data showing that the major phenobarbital inducible cytochromes P-450 (cytochrome P-450IIB1 and cytochrome P-450IIB2) were phosphorylated in intact hepatocytes. This phosphorylation was greatly increased by the cAMP derivatives N6-dibutyryl-cAMP and 8-thiomethyl-cAMP mediated by a cAMP-dependent protein kin...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/10.1.225
更新日期:1989-01-01 00:00:00
abstract::A quantitative relationship was established for 26 nitrosamines between their carcinogenic effectiveness in experimental animals and their mutagenic activity in a mammalian cell-mediated assay. Mutagenesis was measured in Chinese hamster V79 cells co-cultivated with primary rat hepatocytes, which are capable of activa...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/2.10.1075
更新日期:1981-01-01 00:00:00
abstract::Formation of O6-ethylguanine (O6EG) in trachea DNA was measured 12 h after acute i.p. administration of 50, 100 and 200 mg diethylnitrosamine (DEN)/kg body wt to Syrian golden hamsters. Purine bases were fractionated by h.p.l.c., and ethylated guanines were quantified optically by fluorescence spectrophotometry. Signi...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/7.9.1457
更新日期:1986-09-01 00:00:00
abstract::Benzene is a well-characterized human carcinogen and clastogen still present in both the occupational and general environment. However, the levels of benzene encountered today are, in most cases, relatively low and new methods, more specific and sensitive than classical cytogenetics, are probably needed to assess if c...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/18.4.817
更新日期:1997-04-01 00:00:00
abstract::Epithelial cells derived from 46 human breast tissue samples of patients suffering from breast cancer have been cultivated. Twenty-five of these cell cultures stemmed from normal and 21 from tumor tissues. Moderate to large variations of protein levels of three protein kinase C (PKC) isoenzymes (alpha, delta and epsil...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/15.2.359
更新日期:1994-02-01 00:00:00
abstract::Adipocytokines are a group of adipocyte-secreted proteins that have significant effects on the metabolism of lipids and carbohydrates, as well as numerous other processes. A number of recent studies have indicated that some adipocytokines may significantly influence the proliferation of malignant cells in vitro, where...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/bgn080
更新日期:2008-05-01 00:00:00
abstract::N-Acetoxyarylamines are reactive metabolites that lead to arylamine adduct formation with biological macromolecules. A series of 7-substituted-N-hydroxy-2-acetylaminofluorenes were converted to reactive N-acetoxyarylamines by enzymatic N,O-acyltransfer in the presence of DNA. The N-arylhydroxamic acid substrates that ...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/14.8.1651
更新日期:1993-08-01 00:00:00
abstract::Amino acids (AAs) are biologically important nutrient compounds necessary for the survival of any cell. Of the 20 AAs, cancer cells depend on the uptake of several extracellular AAs for survival. However, which extracellular AA is indispensable for the survival of cancer cells and the molecular mechanism involved have...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/bgy033
更新日期:2018-05-28 00:00:00
abstract::Dehydroepiandrosterone sulfate (DHEAS) is the most abundant adrenal steroid with apparent anticarcinogenic properties. Given our recent observation of the dehydro-epiandrosterone-mediated inhibition of protein isoprenylation and the fact that 99% of the circulating dehydro-epiandrosterone is sulfated, with less than 1...
journal_title:Carcinogenesis
pub_type: 杂志文章,收录出版
doi:10.1093/carcin/15.11.2649
更新日期:1994-11-01 00:00:00
abstract::Azido-IQ (2-azido-3-methylimidazo[4,5-f]quinoline), a novel analog of the food mutagen and carcinogen IQ (2-amino-3-methylimidazo[4,5-f]quinoline) was synthesized and characterized. Both thermolysis and photolysis of this azide yield a short-lived nitrene which can react as an electrophile either directly or via proto...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/9.5.869
更新日期:1988-05-01 00:00:00
abstract::Observational studies suggest that fish consumption is associated with a decreased colorectal cancer (CRC) risk. A possible mechanism by which fish could reduce CRC risk is by decreasing colonic genotoxicity. However, concerns have also been raised over the levels of toxic compounds found in mainly oil-rich fish, whic...
journal_title:Carcinogenesis
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1093/carcin/bgp255
更新日期:2010-06-01 00:00:00
abstract::The physiological state of pregnancy confers significant resistance to polycyclic aromatic hydrocarbon (PAH)-induced mammary tumorigenesis. We have tested the abilities of primary mammary cells from pregnant and virgin rats cultured on collagen-coated plates to metabolize PAHs and convert these carcinogens to mutageni...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/5.1.103
更新日期:1984-01-01 00:00:00
abstract::3-Methyladenine DNA glycosylases initiate base excision repair by flipping the nucleotide bearing the target base out of double-stranded DNA into an active site pocket for glycosylic bond cleavage and base release. Substrate bases for the murine 3-methyladenine DNA glycosylase (other than 3-methyladenine) include hypo...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/21.5.901
更新日期:2000-05-01 00:00:00
abstract::Precursor T-cell lymphoblastic neoplasms are aggressive malignancies in need for more effective and specific therapeutic treatments. A significant fraction of these neoplasms harbor deletions on the locus 9p21, targeting the tumor suppressor CDKN2A but also deleting the aconitase 1 (ACO1) gene, a neighboring housekeep...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/bgz185
更新日期:2020-08-12 00:00:00
abstract::Results of previous serologic studies on the association of human papillomavirus (HPV) with esophageal squamous cell carcinoma (ESCC) have been inconsistent. From 2007 to 2010, the authors collected blood samples and relevant demographic data from 1435 patients with ESCC and 2071 age- and sex-matched normal controls f...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/bgt483
更新日期:2014-04-01 00:00:00
abstract::Alterations in the pattern of epidermal cell differentiation and proliferation in mouse skin and benign skin tumors were studied by two-color immunofluorescence using monospecific antibodies. Replicating cells were identified by 5-bromo-deoxyuridine (BrdU) pulse-labeling and differentiating cells by keratins K1 and K1...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/12.11.2063
更新日期:1991-11-01 00:00:00
abstract::Breast cancer incidence is increased in women with both high and low birth weight. The latter is also associated with hyperglycaemia, insulin resistance and type-2 diabetes, each of which independently increases breast cancer risk. We showed previously in our model of poor early-growth that pregnancy estradiol levels ...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/bgl166
更新日期:2007-03-01 00:00:00
abstract::Colorectal cancer is the second leading cause of cancer deaths worldwide with diet playing a prominent role in disease initiation and progression. Flavonoids are secondary plant compounds that are suggested as protective ingredients of a diet rich in fruits and vegetables. We here tested whether flavone, a flavonoid t...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/bgm040
更新日期:2007-07-01 00:00:00
abstract::The hedgehog pathway plays a critical role in the development of the foregut. Recent studies indicate that the hedgehog pathway activation occurs in the stomach and other gastrointestinal cancers. However, the association of hedgehog pathway activation with tumor stage, differentiation and tumor subtype is not well do...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/bgi130
更新日期:2005-10-01 00:00:00
abstract::Dacarbazine (DTIC) is an antitumor agent, used for the treatment of metastatic melanoma. It is metabolized to an alkylating agent which reacts with DNA. A fast and simple method was developed in order to measure drug-induced DNA damage in lymphocytes isolated from frozen blood samples of treated patients. The level of...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/12.6.1153
更新日期:1991-06-01 00:00:00