Abstract:
:We compared the mitogenic and signaling pathways of three Fibroblast Growth Factor Receptors (FGFRs), FGFR1, KGFR and FGFR4 in the same cell line. Each receptor was expressed in L6E9 rat myoblasts that do not normally express detectable levels of FGFRs and clones that express comparable levels of each receptor were selected. Our results show that FGFs induce an effective survival and growth of FGFR1 and KGFR expressing cells. In addition, these cells exhibit a morphology that is reminiscent of that of malignantly transformed cells and display anchorage independent growth in a ligand dependent manner. Unlike KGFR and FGFR1, FGFR4 mediates a less effective growth, and cells overexpressing this receptor do not undergo any morphological changes nor do they display an anchorage independent growth in response to FGFs. All three receptors exhibit both quantitative and qualitative differences in their ability to induce tyrosine phosphorylation of cellular substrates. Both FGFR1 and KGFR induce strong phosphorylation of phospholipase C-gamma and a 90 kDa protein, while FGFR4 induces a relatively weak phosphorylation of phospholipase C-gamma and completely fails to induce phosphorylation of the 90 kDa. The three receptors also induce phosphorylation of the mitogen activated protein kinases (MAPK) but the effect of FGFR1 is far stronger than that of the other two receptors. Since FGFR4 is expressed in myoblasts in vivo, we examined whether this receptor can function in the differentiation pathway of myoblasts. Contrary to its weak mitogenic activity, FGFR4 effectively mediates the inhibition of myogenic differentiation in L6E9 cells and also suppresses the expression of the myogenic regulatory protein myogenin. Taken together, our results suggest that the signaling mechanism of FGFR4 differs from that of FGFR1 and KGFR, and that the primary role of FGFR4 in myoblasts may be the maintenance of their non differentiated state.
journal_name
Oncogenejournal_title
Oncogeneauthors
Shaoul E,Reich-Slotky R,Berman B,Ron Dsubject
Has Abstractpub_date
1995-04-20 00:00:00pages
1553-61issue
8eissn
0950-9232issn
1476-5594journal_volume
10pub_type
杂志文章相关文献
ONCOGENE文献大全abstract::Mutation induction in directly exposed cells is currently regarded as the main component of the genetic risk of ionizing radiation for humans. However, recent data on the transgenerational increases in mutation rates in the offspring of irradiated parents indicate that the genetic risk could be greater than predicted ...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1209723
更新日期:2006-11-30 00:00:00
abstract::We have cloned the rat homolog of the human leukocyte common antigen-related gene (LAR), which encodes a transmembrane receptor phosphotyrosine phosphatase, and raised antibodies against its protein product. We present evidence here for a processing event resulting in a two-chain structure of the mature receptor on th...
journal_title:Oncogene
pub_type: 杂志文章
doi:
更新日期:1992-06-01 00:00:00
abstract::tal-1 deletions are caused by a site specific recombination, which exclusively occurs in 12-26% of T-cell acute lymphoblastic leukemias (T-ALL). In a previous study on a large series of T-ALL we demonstrated an apparent preferential occurrence of tal-1 deletions in CD3- and CD3+ alpha beta lineage T-ALL with TcR-delta...
journal_title:Oncogene
pub_type: 杂志文章
doi:
更新日期:1994-07-01 00:00:00
abstract::Adhesion to the extracellular matrix (ECM) is critical for epithelial tissue homeostasis and function. ECM detachment induces metabolic stress and programmed cell death via anoikis. ECM-detached mammary epithelial cells are able to rapidly activate autophagy allowing for survival and an opportunity for re-attachment. ...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2012.512
更新日期:2013-10-10 00:00:00
abstract::The intrinsic mitochondrial apoptotic pathway acts through two core pro-apoptotic proteins Bax (Bcl2-associated X protein) and Bak (Bcl2-antagonist/killer 1). Although Bax and Bak seem to have redundant roles in apoptosis, accumulating evidence also suggests that they might not be interchangeable under certain conditi...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2011.497
更新日期:2012-06-28 00:00:00
abstract::Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer among men in the developed world. There is a need, for both clinical and scientific reasons, to find markers to identify patients with aggressive disease as early as possible, and to understand the events leading to malignant transformation ...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1207345
更新日期:2004-04-01 00:00:00
abstract::Loss of the DNA mismatch repair (MMR) protein MSH3 leads to the development of a variety of tumors in mice without significantly affecting survival rates, suggesting a modulating role for the MutSβ (MSH2-MSH3) complex in late-onset tumorigenesis. To better study the role of MSH3 in tumor progression, we crossed Msh3(-...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2013.365
更新日期:2014-07-24 00:00:00
abstract::The human RON and its mouse homologue stk are members of the MET family of tyrosine kinase receptors. We have previously shown that the RON gene is over-expressed in human breast carcinomas. As cat mammary tumours have been proposed as a suitable model for aggressive human breast cancer, we identified the feline stk g...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1205221
更新日期:2002-03-07 00:00:00
abstract::Replacement of leucine 301 in the human colony stimulating factor 1 receptor (CSF-1R) by serine, threonine, glutamic acid, or proline induced ligand-independent transforming activity in mouse NIH3T3 cells, whereas substitution by phenylalanine, methionine, cysteine, or lysine did not. Serine, glutamic acid, and prolin...
journal_title:Oncogene
pub_type: 杂志文章
doi:
更新日期:1990-01-01 00:00:00
abstract::The current histoclinical breast cancer classification is simple but imprecise. Several molecular classifications of breast cancers based on expression profiling have been proposed as alternatives. However, their reliability and clinical utility have been repeatedly questioned, notably because most of them were derive...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2011.301
更新日期:2012-03-01 00:00:00
abstract::BRAF mutations occur in ~10% of colorectal cancer (CRC) and are associated with poor prognosis. Inhibitors selective for the BRAFV600E oncoprotein, the most common BRAF mutant, elicit only poor response rates in BRAF-mutant CRC as single agents. This unresponsiveness was mechanistically attributed to the loss of negat...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/s41388-017-0063-5
更新日期:2018-03-01 00:00:00
abstract::Overexpression of members of the myc family of oncogenes contributes to the development of many vertebrate malignancies. Although several functions for myc gene products have been proposed, the targets for Myc activity during oncogenesis or normal development remain to be identified. Oocytes of Xenopus laevis, which a...
journal_title:Oncogene
pub_type: 杂志文章
doi:
更新日期:1992-11-01 00:00:00
abstract::Sal-like protein 4 (SALL4), an embryonic stem cell transcriptional regulator, is re-expressed by an unknown mechanism in poor prognosis hepatocellular carcinoma (HCC), often associated with chronic hepatitis B virus (HBV) infection. Herein, we investigated the mechanism of SALL4 re-expression in HBV-related HCCs. We p...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2016.399
更新日期:2017-04-27 00:00:00
abstract::The metastasis-associated protein 1 (MTA1) is overexpressed in various human cancers and is closely connected with aggressive phenotypes; however, little is known about the transcriptional regulation of the MTA1 gene. This study identified the MTA1 gene as a target of p53-mediated transrepression. The MTA1 promoter co...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2012.2
更新日期:2012-12-06 00:00:00
abstract::The human cellular homolog of v-rel, the transforming gene of reticuloendotheliosis virus, strain T, was previously localized to 2 cent-2p13 by a combination of somatic cell hybrid and in situ hybridization analyses. In this study, we use translocation chromosome analysis to refine c-rel's genetic assignment to 2p12-2...
journal_title:Oncogene
pub_type: 杂志文章
doi:
更新日期:1988-05-01 00:00:00
abstract::We isolated genomic clones of two isotypes of human NDP kinase, nm23-H1 and H2. The nm23-H1 and H2 genes located in a tandem array contained 5 exons and most of the splicing sites in the exon-intron junctions of two isotypes were essentially identical. The regulatory elements of nm23-H1 and H2 genes were also analysed...
journal_title:Oncogene
pub_type: 杂志文章
doi:
更新日期:1996-11-07 00:00:00
abstract::Recent explosive advances in next-generation sequencing technology and computational approaches to massive data enable us to analyze a number of cancer genome profiles by whole-genome sequencing (WGS). To explore cancer genomic alterations and their diversity comprehensively, global and local cancer genome-sequencing ...
journal_title:Oncogene
pub_type: 杂志文章,评审
doi:10.1038/onc.2015.90
更新日期:2015-12-03 00:00:00
abstract::Each step in the synthesis of functional transcript by RNA polymerase II provides a level at which gene expression can be regulated. Control over the elongation phase of transcription is a recognized regulatory mechanism in prokaryotes; however, only recently have examples of conditional transcription elongation block...
journal_title:Oncogene
pub_type: 杂志文章,评审
doi:
更新日期:1990-06-01 00:00:00
abstract::RING-finger proteins play crucial roles in ubiquitination events involved in diverse cellular processes including signal transduction, differentiation and apoptosis. Most of the RING-finger proteins have E3-ubiquitin ligase activity. RNF11 is a small RING-finger protein and harbors a RING-H2 domain and a PY motif that...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1207319
更新日期:2004-03-11 00:00:00
abstract::Signet-ring cell carcinoma is classified in poorly differentiated adenocarcinoma with an aggressive nature and a poor prognosis. We have shown that the activation of PI 3-kinase in highly differentiated adenocarcinomas induces loss of cell-cell contact and formation of vacuoles, giving phenotypes similar to those of s...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1206796
更新日期:2003-08-28 00:00:00
abstract::Chronic lymphocytic leukemia (CLL) is the most common leukemia in the Western world and remains incurable with conventional chemotherapy treatment approaches. CLL as a disease entity is defined by a relatively parsimonious set of diagnostic criteria and therefore likely constitutes an umbrella term for multiple relate...
journal_title:Oncogene
pub_type: 杂志文章,评审
doi:10.1038/onc.2012.411
更新日期:2013-06-06 00:00:00
abstract::Genetic and biochemical evidence suggest that conserved region 3 (CR3) of the adenovirus Ela polypeptide can provide two distinct and separable functions: an N-terminal transcriptional activation region and a C-terminal promoter targeting region. It is thought that the promoter targeting region of Ela CR3 interacts wi...
journal_title:Oncogene
pub_type: 杂志文章
doi:
更新日期:1994-12-01 00:00:00
abstract::Blockade of the mitogen-activated protein (MAP) kinase pathway suppresses growth of colon cancer in vivo. Here we demonstrate a direct link between the extracellular signal-regulated kinase ERK2 and the growth-promoting cell adhesion molecule, integrin alphavbeta6, in colon cancer cells. Down-regulation of beta6 integ...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1205286
更新日期:2002-02-21 00:00:00
abstract::Nuclear-targeted high molecular weight 24 kDa fibroblast growth factor 2 (FGF-2) may induce specific cell functions through intracrine mechanisms. The role of nuclear FGF-2 on the metastatic potential of carcinoma cells was examined by conditional FGF-2 expression, which demonstrated that spontaneous metastasis in nud...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1207638
更新日期:2004-06-10 00:00:00
abstract::Cell migration is an integral component of metastatic disease. The ability of cells to transit between mesenchymal and amoeboid modes of migration has complicated the development of successful therapies designed to target cell migration as a means of inhibiting metastasis. Therefore, investigations of the mechanisms t...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2010.516
更新日期:2011-03-10 00:00:00
abstract::In lung cancer, frequent loss of one allele of chromosome 3p is seen in both small cell lung cancer and non-small cell lung cancer (NSCLC), providing evidence of tumor suppressor genes (TSGs) in this chromosomal region. The mechanism of Fus1 tumor suppressor activity is unknown. We have found that a Fus1 peptide inhib...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1210500
更新日期:2007-10-25 00:00:00
abstract::To study the interplay of steroid hormones and oncogenes in the control of endometrial cell proliferation and differentiation we have generated cell lines derived from rat endometrium by expressing the immortalizing oncogenes adeno E1A or SV40 large T antigen. These lines are positive for mesenchymal markers and conta...
journal_title:Oncogene
pub_type: 杂志文章
doi:
更新日期:1993-08-01 00:00:00
abstract::There is currently a great interest in delayed chromosomal and other damaging effects of low-dose exposure to a variety of pollutants which appear collectively to act through induction of stress-response pathways related to oxidative stress and ageing. These have been studied mostly in the radiation field but evidence...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1209399
更新日期:2006-06-08 00:00:00
abstract::Signal transduction and activator of transcription 3(STAT3) signaling is constitutively activated in various tumors, and is involved in cell survival and proliferation during oncogenesis. There are few reports, however, on the role of STAT3 signaling in gastric cancer. The aim of the present study was to clarify the r...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1207606
更新日期:2004-06-17 00:00:00
abstract::Treatment of fibroblasts with the phorbol ester, 12-O-tetradecanoyl phorbol 13-acetate (TPA), specifically inhibits fibroblast growth factor-2 (FGF-2) induced proliferation. TPA treatment has little or no effect on FGF receptor activation but specifically inhibits the activation of p38 MAPK but not other downstream si...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1205268
更新日期:2002-03-27 00:00:00