Abstract:
:The transforming growth factor-beta (TGF-beta) family of cytokines regulates cell proliferation, morphogenesis, and specialized cell functions in metazoans. Herein, we screened a compound library for modifiers of TGF-beta signaling in NMuMG epithelial cells using a cell-based assay to measure Smad2/3 nuclear translocation. We identified five enhancers of TGF-beta signaling that share a core structure of diethyl 2-(anilinomethylene)malonate (DAM), and D(50) values of 1 to 4 micromol/L. Taking advantage of the Mgat5 mutant phenotype of accelerated receptor loss to endocytosis, we determined that DAM-1976 restored the sensitivity of Mgat5(-/-) carcinoma cells to both TGF-beta and epidermal growth factor (EGF). In Mgat5 mutant and wild-type carcinoma cells, DAM-1976 enhanced and prolonged TGF-beta- and EGF-dependent Smad2/3 and Erk activation, respectively. DAM-1976 reduced ligand-dependent EGF receptor endocytosis, actin microfilament turnover, and cell spreading, suggesting that the compound attenuates vesicular trafficking. Hyperactivation of intracellular signaling has the potential to suppress tumor cell growth and, in this regard, DAM-1976 represents a new pharmacophore that increases basal activation of Smad2/3 and Erk, inhibits microfilament remodeling, and suppresses carcinoma cell growth.
journal_name
Cancer Resjournal_title
Cancer researchauthors
Park HJ,Partridge E,Cheung P,Pawling J,Donovan R,Wrana JL,Dennis JWdoi
10.1158/0008-5472.CAN-05-2542subject
Has Abstractpub_date
2006-04-01 00:00:00pages
3558-66issue
7eissn
0008-5472issn
1538-7445pii
66/7/3558journal_volume
66pub_type
杂志文章相关文献
CANCER RESEARCH文献大全abstract::Immunostimulatory CpG oligodeoxynucleotides (ODNs) can enhance the therapeutic effect of monoclonal antibodies (mAbs) by enhancing antibody-dependent cell-mediated cytotoxicity (ADCC). Distinct classes of CpG ODNs have been found recently to stimulate different effector cell populations. We used murine cancer models t...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:2003-09-01 00:00:00
abstract::Cross-coupling of active protein-1 (AP-1) and nuclear factor (NF)-kappaB has been reported. In the present study, we investigated the possibility that both of these two transcription factors might contribute to the process of tumor promoter-induced transformation. To establish a stable reporter cell system, two report...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1997-08-15 00:00:00
abstract::Specific pathogen-free cats were immunized with an inactivated feline oncornavirus tumor cell vaccine. Immunized cats produced high antibody titers to the feline oncornavirus-associated cell membrane antigen and were protected from oncogenic feline sarcoma virus challenge. However, immunization did not produce virus-n...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1976-10-01 00:00:00
abstract::The purpose of these studies was to select in vitro tumor cells that were resistant to macrophage-mediated lysis. Seven different heterogeneous murine neoplasms (four fibrosarcomas, a melanoma, a rhabdomyosarcoma, and an osteogenic sarcoma) and one cloned line of a fibrosarcoma were incubated in vitro with syngeneic t...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1985-01-01 00:00:00
abstract::Fatty acid synthase (FASN) is the terminal enzyme in de novo lipogenesis and plays a key role in cell proliferation. Pharmacologic inhibitors of FASN are being evaluated in clinical trials for treatment of cancer, obesity, and other diseases. Here, we report a previously unknown mechanism of FASN regulation involving ...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-16-1597
更新日期:2016-12-01 00:00:00
abstract::Nucleolar antigens of normal rat liver, regenerating liver, and Novikoff ascites hepatoma cells were transplanted in vitro from polyadenylic acid-containing messenger RNAs isolated from the respective tissues and immunoprecipitated with specific antinucleolar antibodies and Protein A. By two-dimensional gel electropho...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1983-05-01 00:00:00
abstract::Pancreatic cancers with aberrant expression of macrophage migration inhibitory factor (MIF) are particularly aggressive. To identify key signaling pathways that drive disease aggressiveness in tumors with high MIF expression, we analyzed the expression of coding and noncoding genes in high and low MIF-expressing tumor...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-15-2841
更新日期:2016-07-01 00:00:00
abstract::Neuroblastoma is the most common childhood solid tumor, yet the prognosis for high-risk disease remains poor. We demonstrate here that arginase 2 (ARG2) drives neuroblastoma cell proliferation via regulation of arginine metabolism. Targeting arginine metabolism, either by blocking cationic amino acid transporter 1 (CA...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-18-2139
更新日期:2019-02-01 00:00:00
abstract::The human breast cancer (Br-10) serially transplanted to nude mice (BALB/c-nu/nu) grew well in female mice but very slowly or not at all in untreated male mice and female mice treated with 1 mg of testosterone i.m. twice a week. The growth in female mice was arrested by ovariectomy, and that in male mice was accelerat...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1977-09-01 00:00:00
abstract::In order to explain the heterogeneity of Ca antigen (Ca) expression observed previously on human malignant cells, a relationship of antigen content with events in the cell cycle was studied by multiparameter flow cytometry on four continuous human cell lines, HeLaS3, C4l, HT29, and T24, grown exponentially in culture....
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1984-10-01 00:00:00
abstract::This report describes the application of a new approach, the universal response surface approach, to the quantitative assessment of drug interaction, i.e., the determination of synergism, antagonism, additivity, potentiation, inhibition, and coalitive action. The specific drug combination and experimental growth syste...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1990-09-01 00:00:00
abstract::The evidence for tumor suppressor genes at 8p is well supported by many somatic deletion studies and genetic linkage studies. However, it remains a challenge to pinpoint the tumor suppressor genes at 8p primarily because the implicated regions are broad. In this study, we attempted to narrow down the implicated region...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-06-4570
更新日期:2007-05-01 00:00:00
abstract::We generated DNA expression vectors encoding the full-length neu cDNA (designated pNeuN), the neu extracellular domain (pNeuE), or the neu extracellular and transmembrane domains (pNeuTM). The 293 cells transfected with pNeuN or pNeuTM expressed the neu extracellular domain on the surface membrane, whereas 293 cells t...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1998-05-01 00:00:00
abstract::In the present study, we report the characterization of the p53 tumor suppressor pathway in the 60 cell lines of the National Cancer Institute (NCI) anticancer drug screen, as well as correlations between the integrity of this pathway and the growth-inhibitory potency of 123 anticancer agents in this screen. Assessmen...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1997-10-01 00:00:00
abstract::c-myc expression, amplification, and rearrangement were studied in neoplastic hepatic nodules of rats after diethylnitrosamine treatment, in hepatocellular carcinomas induced by N-methyl-N-nitrosourea, and in tumorigenic liver cell lines derived from rat hepatocytes transformed by diethylnitrosamine in vivo. Steady-st...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1989-12-01 00:00:00
abstract::The process of monoclonal antibody (MAb) binding to tumor cells is greatly influenced by the biology of the respective antigen. This was concluded from an analysis of binding and release of MAbs and MAb fragments to melanoma cells at different concentration levels and different temperatures. With an antigen known to b...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1986-08-01 00:00:00
abstract::Antigens in human adult feces related to carcinoembryonic antigen (CEA) were analyzed with respect to their molecular masses, CEA domain compositions, and N-terminal amino acid sequences. By avoiding perchloric acid treatment, new fecal antigens related to CEA were identified. The fecal antigens revealed by Western bl...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1992-08-01 00:00:00
abstract::The cell line AR230 was established from the peripheral blood mononuclear cells of a patient with chronic myeloid leukemia and t(9;22) translocation bearing a variant type of BCR/ABL rearrangement. AR230 expresses a BCR/ABL fusion protein with a molecular mass of 230 kilodaltons (kDa) due to the insertion of 180 amino...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1995-07-15 00:00:00
abstract::Twenty-eight patients with metastatic malignant melanoma received anti-p97 murine monoclonal antibody (96.5) infused over 2 h at doses between 1 and 20 mg coupled to either 2.5 or 5.0 mCi of 111In by the bifunctional chelating agent diethyltriaminepentaacetic acid. Clearance of 111In from plasma closely fit an open, o...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1985-05-01 00:00:00
abstract::The ShcA adaptor protein transduces oncogenic signals downstream of receptor tyrosine kinases. We show here that breast tumors engage the ShcA pathway to increase their metabolism. ShcA signaling enhanced glucose catabolism through glycolysis and oxidative phosphorylation, rendering breast cancer cells critically depe...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-17-3696
更新日期:2018-09-01 00:00:00
abstract::Aberrant signal transduction has been implicated in malignant transformation, growth, and progression. This has led to the proposal to use inhibitors of signal transduction pathways to treat cancer. One approach to circumventing potential toxicity and improving efficacy would be to target pathways upon which cancer ce...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1992-06-01 00:00:00
abstract::Recent advances in animal modeling, imaging technology, and functional genomics have permitted precise molecular observations of the metastatic process. However, a comprehensive understanding of the premetastatic niche remains elusive, owing to the limited tools that can map subtle differences in molecular mediators i...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-16-1862
更新日期:2017-01-15 00:00:00
abstract::Infection of tumor cells by herpes simplex virus 1 (HSV-1) results in cell destruction and production of progeny virion in a process referred to as viral oncolysis. In this study, an HSV-1 mutant (HSV1yCD) was engineered such that the viral ribonucleotide reductase gene is disrupted by sequences encoding yeast cytosin...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:2001-07-15 00:00:00
abstract::Alkaline phosphatase activity in human endometrial cancer cells of the estrogen-responsive Ishikawa line was markedly stimulated (3-20-fold in 4 days) by estrogens, 5 alpha-dihydrotestosterone, and dehydroepiandrosterone but not by testosterone, medroxyprogesterone acetate, glucocorticoids, several peptide hormones, p...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1986-06-01 00:00:00
abstract::Prostate tumor cells, which characteristically metastasize to bone, initiate binding interactions with bone marrow endothelium under blood flow conditions through binding interactions with E-selectin. We hypothesized that E-selectin ligands on prostate tumor cells are directly associated with bone-metastatic potential...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-04-4653
更新日期:2005-07-01 00:00:00
abstract::We have measured glutathione content in small tissue samples derived from biopsies of primary and metastatic human colon tumors and from colon cancer cell lines in tissue culture and xenografts in athymic mice. Measurements were performed using an enzymatic cycling assay designed to quantitate extremely low levels of ...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1994-08-01 00:00:00
abstract::The clinically relevant polyamine analogue N(1),N(11)-diethylnorspermine (DENSPM) inhibits cell growth by down-regulating polyamine biosynthesis, up-regulating polyamine catabolism at the level of spermidine/spermine N(1)-acetyltransferase (SSAT), and depleting intracellular polyamine pools. Among human melanoma cell ...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:2003-07-01 00:00:00
abstract::The induction of epidermal ornithine decarboxylase (EC 4.1.1.17) (ODC) following topical application of the tumor-promoting agent 12-O-tetradecanoylphorbol-13-acetate (TPA) to mice can be inhibited by topical application of putrescine, the product of the enzyme. The degree of inhibition depended on both the dose and t...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1980-11-01 00:00:00
abstract::Infection by human papillomaviruses (HPV) leads to the formation of benign lesions, warts, and in some cases, cervical cancer. The formation of these lesions is dependent upon increased expression of proangiogenic factors. Angiogenesis is linked to tissue hypoxia through the activity of the oxygen-sensitive hypoxia-in...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-10-2626
更新日期:2011-02-01 00:00:00
abstract::Diets high in red and processed meats are associated with carcinogenesis of the large intestine, but no prospective study has examined meat and fat intake in relation to cancer of the small intestine. We prospectively investigated meat and fat intakes, estimated from a food frequency questionnaire, in relation to smal...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-08-2015
更新日期:2008-11-15 00:00:00