Abstract:
:Anaplastic lymphoma kinase (ALK) was originally identified from a rare subtype of non-Hodgkin's lymphomas carrying t(2;5)(p23;q35) translocation, where ALK was constitutively activated as a result of a fusion with nucleophosmin (NPM). Aberrant ALK fusion proteins were also generated in inflammatory fibrosarcoma and a subset of non-small-cell lung cancers, and these proteins are implicated in their pathogenesis. Recently, ALK has been demonstrated to be constitutively activated by gene mutations and/or amplifications in sporadic as well as familial cases of neuroblastoma. Here we describe another mechanism of aberrant ALK activation observed in a neuroblastoma-derived cell line (NB-1), in which a short-form ALK protein (ALK(del2-3)) having a truncated extracellular domain is overexpressed because of amplification of an abnormal ALK gene that lacks exons 2 and 3. ALK(del2-3) was autophosphorylated in NB-1 cells as well as in ALK(del2-3)-transduced cells and exhibited enhanced in vitro kinase activity compared with the wild-type kinase. ALK(del2-3)-transduced NIH3T3 cells exhibited increased colony-forming capacity in soft agar and tumorigenicity in nude mice. RNAi-mediated ALK knockdown resulted in the growth suppression of ALK(del2-3)-expressing cells, arguing for the oncogenic role of this mutant. Our findings provide a novel insight into the mechanism of deregulation of the ALK kinase and its roles in neuroblastoma pathogenesis.
journal_name
Oncogenejournal_title
Oncogeneauthors
Okubo J,Takita J,Chen Y,Oki K,Nishimura R,Kato M,Sanada M,Hiwatari M,Hayashi Y,Igarashi T,Ogawa Sdoi
10.1038/onc.2011.616subject
Has Abstractpub_date
2012-11-01 00:00:00pages
4667-76issue
44eissn
0950-9232issn
1476-5594pii
onc2011616journal_volume
31pub_type
杂志文章相关文献
ONCOGENE文献大全abstract::TFAP2C/AP-2γ influences development of the mammary gland and regulates patterns of gene expression in luminal and HER2-amplified breast cancer. The roles of TFAP2C in mammary gland tumorigenesis and in pathways critical to cancer progression remain poorly understood. To gain greater insight into oncogenic mechanisms r...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2015.59
更新日期:2015-12-10 00:00:00
abstract::Previously, we have mimicked human neurofibromatosis type 2 (NF2) in conditional Nf2 mutant (P0Cre;Nf2flox2/flox2) mice. Schwannomas, characteristic for NF2, were found at low frequency in older mice. Here, we report that these mice, upon additional hemizygosity for p53, rapidly develop multiple tumours showing featur...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1207858
更新日期:2004-08-26 00:00:00
abstract::DOI: 10.1038/sj/onc/1205119 ...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1205119
更新日期:2002-01-10 00:00:00
abstract::Human basal cell cancer (BCC) has unique growth characteristics with virtual inability to metastasize. We investigated clonality and genetic progression using p53 mutations as marker. Sampling was done through microdissection of frozen immunohistochemically stained 16 microm slices of tumors. From 11 BCC tumors 78 sam...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1201435
更新日期:1997-08-28 00:00:00
abstract::Liver kinase B1 (LKB1) is mutationally inactivated in Peutz-Jeghers syndrome and in a variety of cancers including human papillomavirus (HPV)-caused cervical cancer. However, the significance of LKB1 mutations in cervical cancer initiation and progress has not been examined. Herein, we demonstrated that, in mouse embr...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2016.290
更新日期:2017-03-02 00:00:00
abstract::Hematopoiesis involves a complex array of growth factors that regulate the survival and proliferation of immature progenitors, influence differentiation commitment, and modulate end-stage cell functions. This mini-review is focused on the role of Stat activation in the development of myeloid cells in response to hemat...
journal_title:Oncogene
pub_type: 杂志文章,评审
doi:10.1038/sj.onc.1203477
更新日期:2000-05-15 00:00:00
abstract::The PI3K/AKT signaling pathway is aberrant in a wide variety of cancers. Downstream effectors of AKT are involved in survival, growth and metabolic-related pathways. In contrast, contradictory data relating to AKT effects on cell motility and invasion, crucial prometastatic processes, have been reported pointing to a ...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2010.421
更新日期:2011-01-27 00:00:00
abstract::The angiogenic peptide adrenomedullin (ADM) has been implicated as a mediator of the increased risk of endometrial hyperplasia and cancer resulting from the use of tamoxifen for the treatment and prevention of breast cancer. ADM has been shown to be induced by tamoxifen in the endometrium and to be a growth factor for...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1205374
更新日期:2002-04-25 00:00:00
abstract::Rho small GTP-binding protein regulates various cell functions, such as formation of stress fibers and focal adhesions, cell motility, membrane ruffling, cytokinesis and smooth muscle contraction in mammalian cells and bud formation in the yeast Saccharomyces cerevisiae. As to the functioning sites of Rho in Saccharom...
journal_title:Oncogene
pub_type: 杂志文章
doi:
更新日期:1995-07-06 00:00:00
abstract::The trans-activator protein Tax of human T-cell leukemia virus type I (HTLV-I) plays an important role in the development of adult T-cell leukemia through, at least in part, its ability to stimulate cell growth. We previously reported that Tax induced cell cycle progression from G0/G1 phase to S and G2/M phases in hum...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1204304
更新日期:2001-04-19 00:00:00
abstract::As tumors grow and invade beyond their homeostatic limits, the tumor cells are subjected to insufficient nutrient and oxygen supplies because of excessive demand for nutrition and oxygen, and insufficient vascularization. We therefore hypothesized that tolerance to nutrient deprivation as well as angiogenesis may be c...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1205737
更新日期:2002-09-05 00:00:00
abstract::Protein kinase C (PKC)ɛ, a member of the novel PKC family, has key roles in mitogenesis and survival in normal and cancer cells. PKCɛ is frequently overexpressed in epithelial cancers, particularly in lung cancer. Using a short-hairpin RNA approach, here we established that PKCɛ is required for non-small cell lung car...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2011.428
更新日期:2012-05-17 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 essential role of prolactin (PRL) in normal mammary gland growth and differentiation has implicated this hormone in the development and progression of breast cancer. Although Stat5 is the best-characterized mediator of PRL signals, PRL also activates multiple other signals, whose roles in normal and pathologic pro...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1210454
更新日期:2007-09-20 00:00:00
abstract::SAP-1 (stomach cancer-associated protein tyrosine phosphatase-1) is a transmembrane-type protein tyrosine phosphatase that has been implicated as a negative regulator of integrin-mediated signaling. The potential role of this enzyme in hepatocarcinogenesis has now been investigated by examining its expression in 32 su...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1206588
更新日期:2003-07-24 00:00:00
abstract::wnt genes encode secretory glycoproteins that have been implicated in growth control and development in mice, frogs and insects. In this report we examine properties of two wnt genes recently identified in the nematode Caenorhabditis elegans. The first gene, Ce-wnt-1, was previously identified by a polymerase chain re...
journal_title:Oncogene
pub_type: 杂志文章
doi:
更新日期:1993-07-01 00:00:00
abstract::Treatment of mouse (12)1/CA cells with adriamycin or irradiation with U.V.C. induces p53-dependent transcription of a beta-galactosidase reporter and the endogenous p21/Waf1/Cip1 gene. Despite the induction of Waf1, the cells arrest only transiently in G1 or G2, then resume growth and eventually undergo apoptosis. In ...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1201104
更新日期:1997-05-29 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
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::Polyomavirus infection of adolescent athymic female mice causes a high incidence of mammary adenocarcinomas. We have examined the role of ovarian hormones, age and mammary gland developmental stage at infection on subsequent tumor induction, viral replication and gene expression. Ovariectomy (OVX) of adolescent mice 1...
journal_title:Oncogene
pub_type: 杂志文章
doi:
更新日期:1995-11-02 00:00:00
abstract::Lysophosphatidic acid (LPA) and sphingosine-1-phosphate (S1P) are extracellular lipid mediators that signal through distinct members of the Edg/LP subfamily of G protein-coupled receptors (GPCRs). LPA and S1P receptors are expressed in almost every cell type and can couple to multiple G proteins (G(i), G(q) and G(12/1...
journal_title:Oncogene
pub_type: 杂志文章,评审
doi:10.1038/sj.onc.1204187
更新日期:2001-03-26 00:00:00
abstract::Integrins are adhesion receptors that mediate both cell-extracellular matrix and cell-cell interactions. It has also been reported that the loss of integrin alpha4 expression might be associated with metastasis in several cancers. However, the molecular mechanism for loss of their expression in cancers has not been ex...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1207470
更新日期:2004-04-22 00:00:00
abstract::In chronic myelogenous leukemia (CML), the oncogene bcr-abl encodes a dysregulated tyrosine kinase that inhibits apoptosis. We showed previously that human erythroleukemia K562 cells are resistant to antineoplastic drug (taxol)-induced apoptosis through the atypical protein kinase C iota isozyme (PKC iota), a kinase d...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1204607
更新日期:2001-08-09 00:00:00
abstract::Triple negative breast cancer (TNBC) refers to tumors that do not express clinically significant levels of estrogen and progesterone receptors, and lack membrane overexpression or gene amplification of ErbB-2/HER2, a receptor tyrosine kinase. Transcriptome and proteome heterogeneity of TNBC poses a major challenge to ...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/s41388-020-01430-9
更新日期:2020-09-01 00:00:00
abstract::G2A is a heptahelical cell surface protein that has recently been described as a potential tumor suppressor, based on its ability to counteract transformation of pre-B cells and fibroblasts by Bcr-Abl, an oncogenic tyrosine kinase. We have isolated cDNAs encoding G2A in the course of screening libraries for clones tha...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1203731
更新日期:2000-08-10 00:00:00
abstract::Despite extensive characterization of the role of the EWS-ETS fusions, little is known about secondary genetic alterations and their clinical contribution to Ewing sarcoma (ES). It has been demonstrated that the molecular structure of EWS-ETS lacks prognostic value. Moreover, CDKN2A deletion and TP53 mutation, despite...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2011.317
更新日期:2012-03-08 00:00:00
abstract::Ki-1 lymphoma is a subtype of human malignant lymphoma characterized by the expression of CD30 (Ki-1) and a peculiar morphology. It is occasionally accompanied by a unique reciprocal chromosomal translocation t(2;5)(p23;q35). A Ki-1 lymphoma cell line, AMS3, was established by maintaining biopsied tumor cells in SCID ...
journal_title:Oncogene
pub_type: 杂志文章
doi:
更新日期:1994-06-01 00:00:00
abstract::MicroRNAs (miRNAs) make up a novel class of gene regulators; they function as oncogenes or tumor suppressors by targeting tumor-suppressor genes or oncogenes. A recent study that analysed a large number of human cancer cell lines showed that miR-330 is a potential tumor-suppressor gene. However, the function and molec...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2009.192
更新日期:2009-09-24 00:00:00
abstract::High-risk papillomavirus type 18 (HPV18) is one of the less represented HPV types in low-grade lesions of the anogenital tract, whereas it occupies the second place in cervical cancer, where it can be found in 16% of the cases worldwide, after HPV16 present in 54% of them. These epidemiological data indicate that HPV1...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2010.246
更新日期:2010-09-09 00:00:00
abstract::An integrative functional genomics study of multiple forms of data are vital for discovering molecular drivers of cancer development and progression. Here, we present an integrated genomic strategy utilizing DNA methylation and transcriptome profile data to discover epigenetically regulated genes implicated in cancer ...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2016.176
更新日期:2017-01-05 00:00:00