Abstract:
:Although activating mutations of fibroblast growth factor receptor 3 (FGFR3) are frequent in bladder tumors, little information is available on their specific effects in urothelial cells or the basis for the observed mutation spectrum. We investigated the phenotypic and signaling consequences of three FGFR3 mutations (S249C, Y375C, and K652E) in immortalized normal human urothelial cells (TERT-NHUC) and mouse fibroblasts (NIH-3T3). In TERT-NHUC, all mutant forms of FGFR3 induced phosphorylation of FRS2alpha and ERK1/2, but not AKT or SRC. PLCgamma1 phosphorylation was only observed in TERT-NHUC expressing the common S249C and Y375C mutations, and not the rare K652E mutation. Cells expressing S249C and Y375C FGFR3 displayed an increased saturation density, related to increased proliferation and viability. This effect was significantly dependent on PLCgamma1 signaling and undetectable in cells expressing K652E FGFR3, which failed to phosphorylate PLCgamma1. In contrast to TERT-NHUC, expression of mutant FGFR3 in NIH-3T3 resulted in phosphorylation of Src and Akt. In addition, all forms of mutant FGFR3 were able to phosphorylate Plcgamma1 and induce morphological transformation, cell proliferation, and anchorage-independent growth. Our results indicate that the effects of mutant FGFR3 are both cell type specific and mutation specific. Mutant FGFR3 may confer a selective advantage in the urothelium by overcoming normal contact inhibition of proliferation.
journal_name
Oncogenejournal_title
Oncogeneauthors
di Martino E,L'Hôte CG,Kennedy W,Tomlinson DC,Knowles MAdoi
10.1038/onc.2009.280subject
Has Abstractpub_date
2009-12-03 00:00:00pages
4306-16issue
48eissn
0950-9232issn
1476-5594pii
onc2009280journal_volume
28pub_type
杂志文章相关文献
ONCOGENE文献大全abstract::Epidermal growth factor receptor (EGFR) family members play pivotal roles in cell proliferation, differentiation and survival. Overexpression and mutations of EGFRs, or aberrant EGFR signaling are commonly associated with the development of various cancers, where constitutive NF-κB activation is often found to promote...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2016.430
更新日期:2017-05-18 00:00:00
abstract::The membrane-anchored MMP-regulator RECK is down regulated in many solid tumors; the extent of RECK down regulation correlates with poor prognosis. Forced expression of RECK in tumor cells results in suppression of angiogenesis, invasion, and metastasis. Studies on the roles and the mechanisms of regulation of the REC...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1208733
更新日期:2005-09-01 00:00:00
abstract::The BRCA1-associated RING domain protein BARD1 acts with BRCA1 in double-strand break repair and ubiquitination. BARD1 plays a role as mediator of apoptosis by binding to and stabilizing p53, and BARD1-repressed cells are resistant to apoptosis. We therefore investigated the mechanism by which BARD1 induces p53 stabil...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1208491
更新日期:2005-05-26 00:00:00
abstract::The RAS/RAF mitogen-activated protein kinase pathway (MAPK) is highly active in many tumor types including the majority of high-grade gliomas and expression of activated RAS or RAF in neural progenitor cells combined with either AKT activation or Ink4a/Arf loss leads to the development of high-grade gliomas in vivo. T...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2010.513
更新日期:2011-03-17 00:00:00
abstract::c-myc is a proto-oncogene essential for cell growth. When activated, its expression can lead to uncontrolled cell proliferation, transformation and tumorigenesis. The cell line tEMmyc4 is a murine myelomonocytic cell line that was established following transformation by v-myc. It has a high level of v-myc expression a...
journal_title:Oncogene
pub_type: 杂志文章
doi:
更新日期:1996-03-21 00:00:00
abstract::The naevoid basal cell carcinoma syndrome (NBCCS) is an autosomal dominant disorder characterized by multiple developmental defects and cancer susceptibility, in particular to basal cell carcinomas (BCCs). Medulloblastomas, primitive neuroectodermal tumours (PNETs) arising in childhood, occur in about 3-5% of NBCCS pa...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1201340
更新日期:1997-07-17 00:00:00
abstract::Glycolysis is critical for cancer stem cell reprogramming; however, the underlying regulatory mechanisms remain elusive. Here, we show that pyruvate dehydrogenase kinase 1 (PDK1) is enriched in breast cancer stem cells (BCSCs), whereas depletion of PDK1 remarkably diminishes ALDH+ subpopulations, decreases stemness-re...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2017.368
更新日期:2018-02-22 00:00:00
abstract::Brn-3a is a transcription factor belonging to the class IV of POU domain transcription factors. It is expressed throughout the peripheral nervous system but especially in postmitotic sensory neurons of dorsal root ganglia. Brn-3a is known to regulate different genes involved in neuronal differentiation and survival. I...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1206635
更新日期:2003-08-21 00:00:00
abstract::Mutations of SMAD4/DPC4 are found in about 60% of human invasive pancreatic ductal adenocarcinomas (PDACs); yet, the manner in which SMAD4 deficiency enhances tumorigenesis remains elusive. Using a Cre-LoxP approach, we generated a mutant mouse carrying a targeted deletion of Smad4 in the pancreas. We showed that the ...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2009.375
更新日期:2010-02-04 00:00:00
abstract::The receptor tyrosine kinase FLT3 is expressed in myeloid and lymphoid progenitor cells. Activating mutations in FLT3 occur in 25-30% of acute myeloid leukaemia (AML) patients. Most common are internal tandem duplications of sequence (ITD) leading to constitutive FLT3-ITD kinase activity with an altered signalling qua...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/s41388-019-0757-y
更新日期:2019-06-01 00:00:00
abstract::Oncofetal genes are expressed in embryos or fetuses, are downregulated or undetectable in adult tissues, and then re-expressed in tumors. Known oncofetal genes, such as AFP, GCB, FGF18, IMP-1 and SOX1, often have important clinical applications or pivotal biological functions. To find new oncofetal-like genes, we used...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2010.451
更新日期:2011-02-10 00:00:00
abstract::In this study, we investigated the regulation of FOXM1 expression by estrogen receptor alpha (ERalpha) and its role in hormonal therapy and endocrine resistance. FOXM1 protein and mRNA expression was regulated by ER-ligands, including estrogen, tamoxifen (OHT) and fulvestrant (ICI182780; ICI) in breast carcinoma cell ...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2010.47
更新日期:2010-05-20 00:00:00
abstract::The Mucin 1 (MUC1) protein is overexpressed in various cancers and mediates chemotherapy resistance. However, the mechanism is not fully understood. Given that most chemotherapeutic drugs disrupt ER homeostasis as part of their toxicity, and MUC1 expression is regulated by proteins involved in ER homeostasis, we inves...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/s41388-020-1225-4
更新日期:2020-04-01 00:00:00
abstract::Silencing of the MLH1 gene by promoter hypermethylation is the mechanism underlying the microsatellite instability (MSI) phenotype in endometrial cancers. However, the profile of CpG methylation in a wide range of MLH1 promoters in endometrial cancers and in the normal endometrium is largely unknown. The present study...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1206365
更新日期:2003-04-17 00:00:00
abstract::Brain-specific angiogenesis inhibitor 1 (BAI1), an orphan G protein-coupled receptor-type seven transmembrane protein, was recently found mutated or silenced in multiple human cancers and can interfere with tumor growth when overexpressed. Yet, little is known about its regulation and the molecular mechanisms through ...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2012.1
更新日期:2012-12-13 00:00:00
abstract::Tumor suppressor p53 functions are downregulated in most cervical cancers, because the product of human papilloma virus (HPV) oncogene E6 binds to and inactivates p53 by promoting its degradation. p73, a p53 homologue, is similar to p53 in structure and function but yet not degraded by HPV E6 gene product. In this stu...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1206908
更新日期:2003-11-20 00:00:00
abstract::The myb family of genes encodes highly homologous nuclear transcription factors that play distinct roles in the development of breast, germ cells and hematoid organs. While the mechanisms associated with the regulation of these genes remain unknown, the transactivation of c-Myb was previously shown to be upregulated b...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1207537
更新日期:2004-05-20 00:00:00
abstract::The E3 ligase S-phase kinase-associated protein 2(Skp2) is overexpressed in human cancers and correlated with poor prognosis, but its contributions to tumorigenesis and chemoresistance in nasopharyngeal carcinoma (NPC) are not evident. Herein we show that Skp2 is highly expressed in NPC tumor tissues and cell lines. K...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/s41388-019-0955-7
更新日期:2019-12-01 00:00:00
abstract::The role of specificity protein 1 (Sp1) in controlling gene expression in lung tumor development and metastasis is not well understood. In this study, we showed that the Sp1 level was highly increased and required for lung tumor growth in transgenic mice bearing Kras-induced lung tumors under the control of doxycyclin...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2011.568
更新日期:2012-08-30 00:00:00
abstract::Millions of somatic mutations have recently been discovered in cancer genomes. These mutations in cancer genomes occur due to internal and external mutagenesis forces. Decoding the mutational processes by examining their unique patterns has successfully revealed many known and novel signatures from whole exome data, b...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/s41388-020-1343-z
更新日期:2020-07-01 00:00:00
abstract::Desmoglein 3 (Dsg3), the pemphigus vulgaris antigen, has recently been shown to be upregulated in squamous cell carcinoma (SCC) and has been identified as a good tumor-specific marker for clinical staging of cervical sentinel lymph nodes in head and neck SCC. However, little is known about its biological function in c...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2013.186
更新日期:2014-05-01 00:00:00
abstract::The extracellular matrix glycoprotein, fibronectin, influences a variety of cellular functions including adhesion, migration, survival, differentiation, and growth. Fibronectin has also been shown to increase the migration and proliferation of human lung carcinoma cells. However, the role of fibronectin in controlling...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1209460
更新日期:2006-07-20 00:00:00
abstract::One of the hallmarks of malignancy is the polarization of tumor-associated macrophages (TAMs) from a pro-immune (M1-like) phenotype to an immune-suppressive (M2-like) phenotype. However, the molecular basis of the process is still unclear. MicroRNA (miRNA) comprises a group of small, non-coding RNAs that are broadly e...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2013.258
更新日期:2014-06-05 00:00:00
abstract::Inhibitor of DNA-binding (Id) proteins prevent cell differentiation, promote growth and sustain tumour development. They do so by binding to E proteins and other transcription factors through the helix-loop-helix (HLH) domain, and inhibiting transcription. This makes HLH-mediated Id protein interactions an appealing t...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2009.56
更新日期:2009-04-30 00:00:00
abstract::Glioblastoma (GBM) is the most aggressive tumor of the brain. NF1, a tumor suppressor gene and RAS-GTPase, is one of the highly mutated genes in GBM. Dysregulated NF1 expression promotes cell invasion, proliferation, and tumorigenesis. Loss of NF1 expression in glioblastoma is associated with increased aggressiveness ...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/s41388-019-0809-3
更新日期:2019-07-01 00:00:00
abstract::The role of poly (ADP-ribose) polymerase 1 (PARP1) in cancer has been extensively studied in the context of DNA repair, leading to clinical trials of PARP1 inhibitors in cancers defective in homologous recombination. However, the DNA repair-independent roles of PARP1 in carcinogenesis and metastasis, particularly in l...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2016.3
更新日期:2016-09-01 00:00:00
abstract::Due to its high proclivity to metastasize, and despite the recent development of targeted and immune therapy strategies, melanoma is still the deadliest form of skin cancer. Therefore, understanding the molecular mechanisms underlying melanoma invasion remains crucial. We previously characterized Tspan8 for its abilit...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/s41388-019-0691-z
更新日期:2019-05-01 00:00:00
abstract::The maintenance cytosine DNA methyltransferase DNMT1 and de novo methyltransferase DNMT3b cooperate to establish aberrant DNA methylation and chromatin complexes to repress gene transcription during cancer development. The expression of DNMT3b was constitutively increased 5-20-fold in hTERT/CDK4-immortalized human bro...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2013.580
更新日期:2015-01-29 00:00:00
abstract::Interleukin-6 (IL-6) inhibits the growth of melanocytes and of early stage melanoma cells, but not that of advanced melanoma cells. The in vitro IL-6 response can be restored in the highly metastatic melanoma B16-F10.9 by addition of recombinant soluble IL-6 receptor alpha-chain (sIL-6R). The F10.9 cells then undergo ...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1201213
更新日期:1997-07-31 00:00:00
abstract::The sirtuins (SIRT 1-7) comprise a family of NAD⁺-dependent protein-modifying enzymes with activities in lysine deacetylation, adenosinediphospho(ADP)-ribosylation, and/or deacylation. These enzymes are involved in the cell's stress response systems and in regulating gene expression, DNA damage repair, metabolism and ...
journal_title:Oncogene
pub_type: 杂志文章,评审
doi:10.1038/onc.2013.120
更新日期:2014-03-27 00:00:00