Abstract:
:Bruton's tyrosine kinase (BTK) is essential for B-cell proliferation/differentiation and it is generally believed that its expression and function are limited to bone marrow-derived cells. Here, we report the identification and characterization of p65BTK, a novel isoform abundantly expressed in colon carcinoma cell lines and tumour tissue samples. p65BTK protein is expressed, through heterogeneous nuclear ribonucleoprotein K (hnRNPK)-dependent and internal ribosome entry site-driven translation, from a transcript containing an alternative first exon in the 5'-untranslated region, and is post-transcriptionally regulated, via hnRNPK, by the mitogen-activated protein kinase (MAPK) pathway. p65BTK is endowed with strong transforming activity that depends on active signal-regulated protein kinases-1/2 (ERK1/2) and its inhibition abolishes RAS transforming activity. Accordingly, p65BTK overexpression in colon cancer tissues correlates with ERK1/2 activation. Moreover, p65BTK inhibition affects growth and survival of colon cancer cells. Our data reveal that BTK, via p65BTK expression, is a novel and powerful oncogene acting downstream of the RAS/MAPK pathway and suggest that its targeting may be a promising therapeutic approach.
journal_name
Oncogenejournal_title
Oncogeneauthors
Grassilli E,Pisano F,Cialdella A,Bonomo S,Missaglia C,Cerrito MG,Masiero L,Ianzano L,Giordano F,Cicirelli V,Narloch R,D'Amato F,Noli B,Ferri GL,Leone BE,Stanta G,Bonin S,Helin K,Giovannoni R,Lavitrano Mdoi
10.1038/onc.2015.504subject
Has Abstractpub_date
2016-08-18 00:00:00pages
4368-78issue
33eissn
0950-9232issn
1476-5594pii
onc2015504journal_volume
35pub_type
杂志文章相关文献
ONCOGENE文献大全abstract::Although there is indirect genetic evidence that MEN1, the gene for multiple endocrine neoplasia type 1, is a tumor suppressor gene, little is known about the MEN1-encoded protein, menin. Menin was stably overexpressed in a well-characterized murine tumor cell line, (valine-12)-RAS-transformed NIH3T3 cells. Menin over...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1203005
更新日期:1999-10-21 00:00:00
abstract::Proliferating cell nuclear antigen (PCNA) has no intrinsic enzymatic function, but functions as a sliding platform to mediate protein interactions with the DNA strand. Many proteins interact with PCNA through a small conserved motif with consensus QxxLxxFF. This work uses Schizosaccharomyces pombe and human cells to a...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1209320
更新日期:2006-05-11 00:00:00
abstract::It is well known that intracellular antioxidant glutathione (GSH) plays major roles in the maintenance of redox status and defense of oxidative stress. Ras, a small GTP-binding protein, may send growth-stimulating message to the nucleus through downstream Rac oncoprotein and superoxide (O(2*-)). These findings led us ...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1206289
更新日期:2003-03-06 00:00:00
abstract::Earlier we showed that RACK1 regulates growth of human colon cells by suppressing Src activity at G(1) and mitotic checkpoints. Here, we show that RACK1 also induces apoptosis of the cells, partly by inhibiting Src. In the intrinsic pathway, RACK1 inhibits expression of anti-apoptotic Bcl-2 and Bcl-X(L), induces expre...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2009.293
更新日期:2009-12-17 00:00:00
abstract::The recent identification of the mouse White spotting and Steel loci as genes encoding the c-kit receptor and its ligand, respectively, has shed light on the importance of this ligand and receptor in embryogenesis, melanogenesis and hematopoiesis. In order to determine if the c-kit proto-oncogene is involved in human ...
journal_title:Oncogene
pub_type: 杂志文章
doi:
更新日期:1992-07-01 00:00:00
abstract::Herpesvirus saimiri is an oncogenic virus causing rapid T-cell lymphomas in New World primates and rabbits. Deletion analysis of one strain of H saimiri has indicated an open reading frame, StpA, necessary for oncongenicity in monkeys. We have investigated the function of StpA in tumor induction by the generation of t...
journal_title:Oncogene
pub_type: 杂志文章
doi:
更新日期:1996-04-18 00:00:00
abstract::We have examined the possibility that the E7 proteins of the high-risk human papillomavirus (HPV) type 16 and 18 and the oncogenic adenovirus (Ad) type 12 E1A protein share the ability to down-regulate the expression of components of the antigen processing and presentation pathway, as a common strategy in the evasion ...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1203860
更新日期:2000-10-05 00:00:00
abstract::Caspases are a family of cysteine proteases expressed as inactive zymogens in virtually all animal cells. These enzymes play a central role in most cell death pathways leading to apoptosis but growing evidences implicate caspases also in nonapoptotic functions. Several of these enzymes, activated in molecular platform...
journal_title:Oncogene
pub_type: 杂志文章,评审
doi:10.1038/sj.onc.1208524
更新日期:2005-08-04 00:00:00
abstract::An oncogenic mutation (G49A:E17K) in the AKT1 gene has been described recently in human breast, colon, and ovarian cancers. The low frequency of this mutation and perhaps other selective pressures have prevented the isolation of human cancer cell lines that harbor this mutation thereby limiting functional analysis. He...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2009.516
更新日期:2010-04-22 00:00:00
abstract::Midkine is a heparin-binding growth factor, originally reported as the product of a retinoic acid-responsive gene during embryogenesis, but currently viewed as a multifaceted factor contributing to both normal tissue homeostasis and disease development. Midkine is abnormally expressed at high levels in various human m...
journal_title:Oncogene
pub_type: 杂志文章,评审
doi:10.1038/s41388-019-1124-8
更新日期:2020-03-01 00:00:00
abstract::Malignant peripheral nerve sheath tumors (MPNSTs) are soft-tissue sarcomas that frequently arise in patients with neurofibromatosis type 1 (NF1). Most of these tumors are unresectable at diagnosis and minimally responsive to conventional treatment, lending urgency to the identification of new pathway dependencies and ...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/s41388-019-0965-5
更新日期:2019-09-01 00:00:00
abstract::Injection of the human neurotropic polyomavirus, JCV, into neonatal hamsters causes tumors of glial origin. Previously, a rapidly proliferating cell line, HJC-15, which expresses high levels of the viral T-antigen, had been established from JCV-induced hamster glial tumors. In our analyses of the mechanisms involved i...
journal_title:Oncogene
pub_type: 杂志文章
doi:
更新日期:1996-03-21 00:00:00
abstract::We identified the chromosome 11q23 region as containing a putative tumour suppressor gene(s) frequently deleted in nonfamilial breast and other cancers. To define this region(s) further, we performed a systematic genetic analysis at chromosome 11q14-qterm in sporadic breast and colorectal cancer. Tumour and constituti...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1200847
更新日期:1997-01-30 00:00:00
abstract::In classical Hodgkin lymphoma the malignant Hodgkin/Reed-Sternberg (HRS) cells characteristically constitute only a small minority of the tumour load. Their origin has been debated for decades, but on the basis of rearrangement and somatic hypermutations of their immunoglubulin (Ig) genes, HRS cells are now ascribed t...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1205629
更新日期:2002-07-25 00:00:00
abstract::Deletions involving chromosome 9 occur in more than 50% of human bladder cancers of all grades and stages. Most involve loss of the whole chromosome or of an entire chromosome arm but some small deletions are found which can be used to define critical regions which may contain tumour suppressor genes. We have localize...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1202854
更新日期:1999-04-22 00:00:00
abstract::A hallmark of human cancer is heterogeneity, reflecting the complex series of changes resulting in the activation of oncogenes coupled with inactivation of tumor suppressor genes. Breast cancer is no exception and indeed, many studies have revealed considerable complexity and heterogeneity in the population of primary...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2011.433
更新日期:2012-05-17 00:00:00
abstract::IL-4 and IL-13 are related cytokines which induce both pro- and anti-inflammatory effects depending on the cell type they act upon and the nature of the receptors expressed. The type I receptor complex is composed of the IL-4Ralpha and gammac and only binds IL-4, whereas, in the type II receptor, IL-4Ralpha dimerizes ...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1204629
更新日期:2001-10-11 00:00:00
abstract::Cbl proteins are ubiquitin protein ligases, which ubiquitinate activated tyrosine kinases and target them for degradation. Both c-Cbl and Cbl-b have an ubiquitin associated (UBA) domain at their C-terminal end. We observed that high molecular weight ubiquitinated proteins constitutively coimmunoprecipitated with trans...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1207952
更新日期:2004-09-16 00:00:00
abstract::In the presence of ERbeta, trans-hydroxytamoxifen (TOT) protects cells against 17beta-estradiol (E(2))-induced oxidative DNA damage (ODD) and this correlates with increased expression of the antioxidative enzyme quinone reductase (QR). Here, we investigate the molecular mechanism responsible for ERbeta-mediated protec...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2008.235
更新日期:2008-10-23 00:00:00
abstract::A series of primary human breast tumors was analysed by immunoblotting with anti-neu antibodies. Overproduction of the neu protein-tyrosine kinase, p185neu, was observed in 23 of 56 malignant tumor samples. 29 of these tumors were also immunoblotted with antiphosphotyrosine antibodies. A single prominent phosphotyrosi...
journal_title:Oncogene
pub_type: 杂志文章
doi:
更新日期:1990-06-01 00:00:00
abstract::A wealth of cytogenetic data has demonstrated that numerous somatic genetic changes are involved in the pathogenesis of human lung cancer. Despite the complexity of the genomic changes observed in these neoplasms, recurrent chromosomal patterns have emerged. In this review, we summarize chromosomal alterations identif...
journal_title:Oncogene
pub_type: 杂志文章,评审
doi:10.1038/sj.onc.1205836
更新日期:2002-10-07 00:00:00
abstract::Genetic mutations in BRCA1, which is crucial for the process of DNA repair and maintenance of genomic integrity, are known to increase markedly the risk of breast and ovarian cancers. Clinical genetic testing has been used to identify new BRCA1 variants; however, functional assessment and determination of their pathog...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/s41388-019-0968-2
更新日期:2020-01-01 00:00:00
abstract::Pancreatic ductal adenocarcinoma (PDAC) is a deadly disease and a major health problem in the United States. While the cytokine TGF-β has been implicated in PDAC development, it can exert both pro-tumorigenic and anti-tumorigenic effects that are highly context dependent and incompletely understood. Using three-dimens...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/s41388-018-0264-6
更新日期:2018-08-01 00:00:00
abstract::Reactive oxygen species, which are prevalent in mitochondria, cause oxidative DNA damage including the mutagenic DNA lesion 7,8-dihydroxyguanine (8-oxoG). Oxidative damage to mitochondrial DNA has been implicated as a causative factor in a wide variety of degenerative diseases, and in cancer and aging. 8-oxoG is repai...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1205994
更新日期:2002-12-12 00:00:00
abstract::The cellular and molecular mechanisms of tumor progression following chemotherapy are largely unknown. Here, we demonstrate that cisplatin (CDDP) treatment upregulates VEGF and Flt1 expression leading to the survival and expansion of a highly tumorigenic fraction of side-population (SP) cells in osteosarcoma (HOS), ne...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2008.38
更新日期:2008-06-26 00:00:00
abstract::We describe the cytogenetic and molecular characterization of a t(1;13)(q22;q12) constitutional rearrangement occurring in a patient with a relatively benign form of neuroblastoma, called ganglioneuroblastoma. Somatic cell hybrids were generated between mouse 3T3 cells and a lymphoblastoid cell line from this patient,...
journal_title:Oncogene
pub_type: 杂志文章
doi:
更新日期:1992-08-01 00:00:00
abstract::REF cells transformed by oncogenes E1A and cHa-ras reveal high and constitutive DNA-binding activity of AP-1 factor lacking in c-Fos protein. Consistently, the transcription of c-fos gene has been found to be downregulated. To elucidate the mechanisms of c-fos downregulation in E1A+cHa-ras transformants, we studied th...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1205118
更新日期:2002-01-24 00:00:00
abstract::Chromosome 8 loss of heterozygosity (LOH) in cancer of the urinary bladder is associated with high tumour grade and stage. We have screened 193 cases of transitional cell carcinoma (TCC) of the bladder using 30 microsatellite polymorphisms on chromosome 8. Forty three cases (22%) showed LOH on 8p, the majority of whic...
journal_title:Oncogene
pub_type: 杂志文章
doi:
更新日期:1996-03-07 00:00:00
abstract::High-throughput, human cell-based applications of RNA-mediated interference (RNAi) have emerged in recent years as perhaps the most powerful of a 'second wave' of functional genomics technologies. The available reagents and methodologies for RNAi screening studies now enable a wide range of different scopes and scales...
journal_title:Oncogene
pub_type: 杂志文章,评审
doi:10.1038/sj.onc.1208072
更新日期:2004-11-01 00:00:00
abstract::We previously reported that overexpression of the 24 kDa basic fibroblast factor (or FGF-2) isoform provides protection from the cytotoxic effect of ionizing radiation (IR). DNA double-strand breaks (DSB), the IR-induced lethal lesions, are mainly repaired in human cells by non-homologous end joining system (NHEJ). NH...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1205838
更新日期:2002-09-19 00:00:00