Abstract:
:ADAMs (a disintegrin and metalloproteinase) have important roles in development and diseases such as cancer. Previously, an ADAM15 splice variant (ADAM15B), which contains an inserted cytoplasmic Src-binding site, was linked to clinical aggressiveness in breast cancer, yet little was known about how this splice variant affects the function of ADAM15. Here, we show that ADAM15B has enhanced catalytic activity in cell-based assays compared with ADAM15A, which lacks a Src-binding site, using shedding of fibroblast growth factor receptor 2iiib variant as an assay for catalytic activity. Moreover, the enhanced activity of ADAM15B compared with ADAM15A depends on Src because it is abolished by Src-kinase inhibitors and in Src(-/-) cells, but not in Src(-/-) cells rescued with Src. These findings provide insights into the mechanism of how a splice variant linked to clinical agressiveness in breast cancer causes increased activity of ADAM15B, and suggest that inhibitors of the ADAM15 protease activity or of the interaction of ADAM15B with Src could be useful to treat breast cancer in patients with dysregulated ADAM15B.
journal_name
Cancer Resjournal_title
Cancer researchauthors
Maretzky T,Le Gall SM,Worpenberg-Pietruk S,Eder J,Overall CM,Huang XY,Poghosyan Z,Edwards DR,Blobel CPdoi
10.1158/0008-5472.CAN-08-4766subject
Has Abstractpub_date
2009-06-01 00:00:00pages
4573-6issue
11eissn
0008-5472issn
1538-7445pii
69/11/4573journal_volume
69pub_type
杂志文章相关文献
CANCER RESEARCH文献大全abstract::Although chemokine and growth factor receptors are attractive and popular targets for cancer therapeutic intervention, structure-based targeting of the ligands themselves is generally not considered practical. New evidence indicates that a notable exception to this is macrophage migration inhibitory factor (MIF). MIF,...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-07-6227
更新日期:2008-09-15 00:00:00
abstract::Tumors of the central nervous system (CNS) often have sustained expression of labile genes, including angiogenic growth factors and immunosuppressive cytokines, which promote tumor progression. Stabilization of the RNA transcripts for these genes, such as vascular endothelial growth factor (VEGF), is an important mole...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:2001-03-01 00:00:00
abstract::Cells with a temperature-sensitive mutant of the v-abl oncoprotein (IC.DP) were treated with the anticancer drugs melphalan or hydroxyurea. At the restrictive temperature for v-ABL protein tyrosine kinase activity, drug-treated IC.DP cells died by apoptosis. In contrast, apoptotic cell death induced by either drug was...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1994-10-01 00:00:00
abstract::Cells that overexpress high-mobility group A1 (HMGA1) proteins exhibit deficient nucleotide excision repair (NER) after exposure to DNA-damaging agents, a condition ameliorated by artificially lowering intracellular levels of these nonhistone proteins. One possible mechanism for this NER inhibition is down-regulation ...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-06-1689
更新日期:2007-07-01 00:00:00
abstract::The tumor suppressor phosphatase and tensin homologue (PTEN) is involved in cell proliferation, adhesion, and apoptosis. PTEN overexpression in mammary epithelium leads to reduced cell number and impaired differentiation and secretion. In contrast, overexpression of the proto-oncogene Wnt-1 in mammary epithelium leads...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-05-0181
更新日期:2005-08-01 00:00:00
abstract::In summary, analysis of the P01 program indicates that differences exist in scores and funding requirements between purely basic and translational P01s; P01 funding has been stable and the P01 policies consistent; growth in average costs for P01s has lagged compared to R01s; P01 grantees have a higher success rate tha...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1993-02-01 00:00:00
abstract::On the basis of reports of rat mammary- and pancreas-tumor models, we hypothesized that an increase in consumption of linoleic acid (LA) would also cause an enhancement in mouse skin-tumor promotion. SEN-CAR mice were placed on diets containing 0.8%, 2.2%, 3.5%, 4.5%, 5.6%, 7.0%, or 8.4% LA, 1 week after initiation wi...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1992-04-01 00:00:00
abstract::Metastasis requires cytoskeletal remodeling for migration, adhesion, and extravasation of metastatic cells. Although protein kinase C (PKC) is involved in tumor promotion/progression and cytoskeletal remodeling, its role in metastasis has not been defined. PKCdelta levels are increased in highly metastatic 13762NF mam...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1999-07-01 00:00:00
abstract::When the human cell line NHIK 3025 was exposed to retinoic acid (1 nM; 10 microM), the cell cycle time was prolonged. Experiments using cells synchronized by mitotic selection showed that the retinoic acid induced growth delay was barely seen within the first cell cycle after exposure to 10 microM retinoic acid, where...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1986-03-01 00:00:00
abstract::Melanoma-derived lipoprotein lipase inhibitor (MLPLI) is a factor purified from the conditioned medium of a human melanoma cell line, SEKI, which induced severe cachexia in tumor-bearing nude mice. Amino acid sequencing revealed that the amino-terminal portion was identical to that of leukemia-inhibitory factor (LIF)....
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1991-12-15 00:00:00
abstract::It has been suggested that oxygen-carrying blood substitutes, perfluorochemical (PFC) emulsions, can increase blood flow and oxygen delivery to poorly perfused tumor regions. Local cerebral blood flow was measured in male Wistar rats bearing intracranial Walker 256 tumor with and without blood-PFC exchange using [14C]...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1987-06-15 00:00:00
abstract::The intermediate filament protein Nestin serves as a biomarker for stem cells and has been used to identify subsets of cancer stem-like cells. However, the mechanistic contributions of Nestin to cancer pathogenesis are not understood. Here, we report that Nestin binds the hedgehog pathway transcription factor Gli3 to ...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-16-1547
更新日期:2016-09-15 00:00:00
abstract::The Notch family of proteins plays an integral role in determining cell fates, such as proliferation, differentiation, and apoptosis. We show that Notch-1 and its ligands, Delta-like-1 and Jagged-1, are overexpressed in many glioma cell lines and primary human gliomas. Immunohistochemistry of a primary human glioma ti...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-04-1890
更新日期:2005-03-15 00:00:00
abstract::Glial tumors progress to malignant grades by heightened proliferation and relentless dispersion throughout the central nervous system. Understanding genetic and biochemical processes that foster these behaviors is likely to reveal specific and effective targets for therapeutic intervention. Our current report shows th...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-06-0418
更新日期:2006-10-01 00:00:00
abstract::In an attempt to develop better combination therapies for use with local radiation, the interaction between bleomycin and hyperthermia +/- radiation was studied in the FSaIIC tumor system. In cells exposed in vitro to bleomycin at 37 degrees C and at pH 7.40, the drug was substantially more toxic toward normally oxyge...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1988-11-15 00:00:00
abstract::DMBT1 is a candidate tumor suppressor gene located at 10q25.3-26.1. Homozygous deletion of the gene was found in a subset of medulloblastoma and glioblastoma multiforme; lack of expression was noted in the majority of these tumors. In adult tissues, DMBT1 is highly expressed only in lung and small intestine tissues, i...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1999-04-15 00:00:00
abstract::Association studies in large series of breast cancer patients can be used to identify single-nucleotide polymorphisms (SNP) contributing to breast cancer susceptibility. Previous studies have suggested associations between variants in TP53 (R72P) and MDM2 (SNP309) and cancer risk. Data from molecular studies suggest a...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-07-0738
更新日期:2007-10-01 00:00:00
abstract::We have examined the properties of the estrogen receptor and progesterone receptor in MDA-MB-134 human breast cells and have evaluated the effects of estrogen on cell proliferation and progesterone receptor levels in these cells as indices of hormonal sensitivity. These cells contain high levels of estrogen receptor (...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1986-03-01 00:00:00
abstract::In cancer cachexia both cardiac and skeletal muscle suffer an important protein mobilization as a result of increased proteolysis. Administration of the beta2-agonist formoterol to both rats and mice bearing highly cachectic tumors resulted in an important reversal of the muscle-wasting process. The anti-wasting effec...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-04-0425
更新日期:2004-09-15 00:00:00
abstract::The proto-oncogene, c-src, has been implicated in the tumorigenesis in breast cancer. However, the relationship of c-src with distant metastasis is unclear. Moreover, the role of c-src in organ-preferential metastasis of breast cancer is unknown. Because breast cancer has a strong predilection for metastasizing to bon...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:2003-08-15 00:00:00
abstract::Three Burkitt's lymphoma cell lines were studied for their response to cis-diamminedichloroplatinum(II) (cis-DDP) and L-phenylalanine mustard (L-PAM) with the objective of relating cytotoxicity to DNA cross-linking in human cells. Cytotoxicity was measured by cell proliferation and colony formation assays. DNA interst...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1982-03-01 00:00:00
abstract::The present study was designed to investigate the effect of selenium supplementation on dimethylbenz[a]anthracene-induced mammary tumorigenesis in female Sprague-Dawley rats fed either a 5 or 25% corn oil diet, denoted as low fat (LF) or high fat (HF), respectively. Selenium supplementation of LF and HF diets were beg...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1981-07-01 00:00:00
abstract::Although a Chinese hamster V79 cell-based assay for inhibitors of metabolic cooperation is currently available, the development of a human cell-based assay is desirable in order to avoid inappropriate extrapolation from animal cells to human cells. Cells derived from a human teratocarcinoma cell line (designated PA-1)...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1986-03-01 00:00:00
abstract::About two thirds of laryngeal cancers originate at the vocal cords. Early-stage detection of malignant vocal fold alterations, including a discrimination of premalignant lesions, represents a major challenge in laryngology as precancerous vocal fold lesions and small carcinomas are difficult to distinguish by means of...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-14-1458
更新日期:2015-01-01 00:00:00
abstract::Mutations of the tumor suppressor E-cadherin and overexpression of the receptor tyrosine kinase epidermal growth factor receptor (EGFR) are among the most frequent genetic alterations associated with diffuse-type gastric carcinoma. Accumulating evidence suggests a functional relationship between E-cadherin and EGFR th...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-07-1588
更新日期:2008-02-01 00:00:00
abstract::Interleukin 4, a T cell-derived 20-kDa glycoprotein, plays an important role in regulating the immune response of B cells, T cells, and macrophages against infections and malignant cells. For this reason recombinant human interleukin 4 (rhIL-4) has entered early clinical trials in cancer patients. In the present study...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1995-05-15 00:00:00
abstract::DNA mismatch binding in vitro, resistance to DNA methylation damage, and spontaneous mutation rates were examined in human colorectal adenocarcinoma cell lines. Of 11 cell lines, 3 (DLD1, HCT15, and LoVo) were defective in mismatch binding. All three lines had a mutator phenotype. These properties indicate that DLD1 a...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1995-06-01 00:00:00
abstract::Tumors often display mechanisms to avoid or suppress immune recognition. One such mechanism is the shedding of gangliosides into the local tumor microenvironment, and a high concentration of circulating gangliosides is associated with poor prognosis. In this study, we identify ganglioside GD3, which was isolated from ...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-11-2695
更新日期:2012-08-01 00:00:00
abstract::The mitochondrial peripheral benzodiazepine receptor (mPBR) is involved in a functional structure designated as the permeability transition pore, which controls apoptosis. Binding of Fas/APO-1/CD95 triggers a prototypic apoptosis-inducing pathway. Using four different human tumor cell lines (T-cell Jurkat, neuroblasto...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:2002-03-01 00:00:00
abstract::The simultaneous distribution of monoclonal 131I-labeled anti-carcinoembryonic antigen (CEA) immunoglobulin (IgG) (NP-2) or 131I-labeled irrelevant myeloma IgG (Ag8) and [3H]thymidine was studied in hamsters bearing transplants of the GW-39 human colon carcinoma by qualitative double-tracer whole-body autoradiography....
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1987-04-15 00:00:00