Abstract:
:As leukemic transformation of myeloproliferative neoplasms (MPNs) worsens the clinical outcome, reducing the inherent risk of the critical event in MPN cases could be beneficial. Among genetic alterations concerning the transformation, the frequent one is TP53 mutation. Here we show that retroviral overexpression of Jak2 V617F mutant into wild-type p53 murine bone marrow cells induced polycythemia vera (PV) in the recipient mice, whereas Jak2 V617F-transduced p53-null mice developed lethal leukemia after the preceding PV phase. The leukemic mice had severe anemia, hepatosplenomegaly, pulmonary hemorrhage and expansion of dysplastic erythroid progenitors. Primitive leukemia cells (c-kit+Sca1+Lin- (KSL) and CD34-CD16/32-c-kit+Sca1-Lin- (megakaryocyte-erythroid progenitor; MEP)) and erythroid progenitors (CD71+) from Jak2 V617F-transduced p53-null leukemic mice had leukemia-initiating capacity, however, myeloid differentiated populations (Mac-1+) could not recapitulate the disease. Interestingly, recipients transplanted with CD71+ cells rapidly developed erythroid leukemia, which was in sharp contrast to leukemic KSL cells to cause lethal leukemia after the polycythemic state. The leukemic CD71+ cells were more sensitive to INCB18424, a potent JAK inhibitor, than KSL cells. p53 restoration could ameliorate Jak2 V617F-transduced p53-null erythroleukemia. Taken together, our results show that p53 loss is sufficient for inducing leukemic transformation in Jak2 V617F-positive MPN.
journal_name
Oncogenejournal_title
Oncogeneauthors
Tsuruta-Kishino T,Koya J,Kataoka K,Narukawa K,Sumitomo Y,Kobayashi H,Sato T,Kurokawa Mdoi
10.1038/onc.2016.478subject
Has Abstractpub_date
2017-06-08 00:00:00pages
3300-3311issue
23eissn
0950-9232issn
1476-5594pii
onc2016478journal_volume
36pub_type
杂志文章相关文献
ONCOGENE文献大全abstract::Metastatic growth in breast cancer (BC) has been proposed as an exclusive property of cancer stem cells (CSCs). However, formal proof of their identity as cells of origin of recurrences at distant sites and the molecular events that may contribute to tumor cell dissemination and metastasis development are yet to be el...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2014.5
更新日期:2015-02-05 00:00:00
abstract::Epithelial-to-mesenchymal transition (EMT) promotes cell motility, which is important for the metastasis of malignant cells, and blocks CD95-mediated apoptotic signaling triggered by immune cells and chemotherapeutic regimens. CD95L, the cognate ligand of CD95, can be cleaved by metalloproteases and released as a solu...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2014.55
更新日期:2015-02-19 00:00:00
abstract::von Hippel-Lindau (VHL) disease is a dominantly inherited family cancer syndrome characterized by the development of retinal and central nervous system haemangioblastomas, renal cell carcinoma (RCC) and phaeochromocytoma. Specific germline VHL mutations may predispose to haemangioblastomas, RCC and phaeochromocytoma t...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1209932
更新日期:2007-03-08 00:00:00
abstract::The steady-state levels of p53 mRNA and protein were barely detectable by Northern and Western blot analysis in spontaneously immortalized (10)3 and (10)7 murine embryo fibroblast (MEF) cells. But when cells were treated with cycloheximide (CHX) or emetine, expression levels were restored to those observed in primary ...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1204423
更新日期:2001-05-31 00:00:00
abstract::Colitis-associated colorectal cancers are an etiologically distinct subgroup of colon cancers that occur in individuals suffering from inflammatory bowel disease and arise as a consequence of persistent exposure of hyperproliferative epithelial stem cells to an inflammatory microenvironment. An intrinsic defect in the...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2011.545
更新日期:2012-08-09 00:00:00
abstract::BAG-1 is a multifunctional protein that interacts with a wide range of cellular targets including heat-shock proteins and some nuclear hormone receptors. BAG-1 exists as three major isoforms, BAG-1L, BAG-1M and BAG-1S. BAG-1L contains a nuclear localization signal, which is not present in the other isoforms, and is pr...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1206688
更新日期:2003-08-07 00:00:00
abstract::RRR-alpha-tocopheryl succinate (alpha-vitamin E succinate, VES), one of the vitamin E derivatives, can effectively inhibit the proliferation of human prostate cancer cells. However, little is known about its effect on prostate cancer cell invasive ability. Tumor metastasis is a complex process and the extracellular ma...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1207435
更新日期:2004-04-15 00:00:00
abstract::The mammalian target of rapamycin (mTOR) is a highly conserved serine-threonine kinase activated in response to growth factors and nutrients. Because of frequent dysregulation of the mTOR signaling pathway in diverse human cancers, this kinase is a key therapeutic target. Redd1 is a negative regulator of mTOR, mediati...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2011.102
更新日期:2011-09-01 00:00:00
abstract::An altered protein expression of Ca(2+)-dependent protein kinase C (PKC) isoforms and a point mutation in the PKC alpha cDNA (position 908 of the nucleotide sequence, position 294 of the amino acid sequence, substitution of an aspartic acid by a glycine) have been previously described in a subpopulation of human pitui...
journal_title:Oncogene
pub_type: 杂志文章
doi:
更新日期:1995-08-17 00:00:00
abstract::Apoptin, a protein of the chicken anemia virus (CAV), represents a novel potential anticancer therapeutic, because it induces apoptotic death specifically in tumor but not normal cells. The cellular localization appears to be crucial for apoptin's selective toxicity. In normal cells apoptin remains in the cytoplasm, w...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1209923
更新日期:2007-03-08 00:00:00
abstract::We have previously shown that transactivation by tumor suppressor protein p53 can be inhibited in vivo at elevated protein concentrations. In this study we characterize the structural requirements of this function. We show that oligomerization domain of p53 is involved in loss of transactivation at high protein concen...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1201749
更新日期:1998-05-07 00:00:00
abstract::Receptor tyrosine kinases of the Eph family are upregulated in several different types of cancer. One family member in particular, the EphA2 receptor, has been linked to breast, prostate, lung and colon cancer, as well as melanoma. However, mechanisms by which EphA2 contributes to tumor progression are far from clear....
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1208937
更新日期:2005-11-24 00:00:00
abstract::Prostate cancer is the second highest cause of cancer-related deaths of men in the US. Signal transducers and activators of transcription (STATs) proteins are a small family of latent cytoplasmic transcription factors that act downstream of Janus kinase (JAK) activation and mediate intracellular signaling from a wide ...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1208437
更新日期:2005-03-17 00:00:00
abstract::Induction of apoptosis by adenovirus E1A in rodent cells is stimulated by wild type (wt) p53 but completely suppressed by mutated p53. The suppression is overcome by coexpression with Id proteins (Ids). The cells expressing E1A and Ids undergo apoptosis after accumulation in S phase, suggesting that S phase events are...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1203063
更新日期:1999-08-26 00:00:00
abstract::Fibronectin extracellular matrix plays a critical role in the microenvironment of cells. Loss of this matrix frequently accompanies oncogenic transformation, allowing changes in cell growth, morphology, and tissue organization. The HT1080 human fibrosarcoma cell line is deficient in formation of fibronectin matrix fib...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1203626
更新日期:2000-06-29 00:00:00
abstract::A common characteristic of malignant cells derived from patients with Hodgkin's disease (HD) is a high level of constitutive nuclear NF-kappaB/Rel activity, which stimulates proliferation and confers resistance to apoptosis. We have analysed the mechanisms that account for NF-kappaB activation in a panel of Hodgkin/Re...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1202351
更新日期:1999-01-28 00:00:00
abstract::The epithelium-specific transcription factor, ERT/ESX/ESE-1/ELF3, binds to the TGF-beta RII promoter in a sequence specific manner and regulates its expression. In this study, we investigated whether ERT could regulate endogenous TGF-beta RII expression in Hs578t breast cancer cells. Analyses of the Hs578t parental ce...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1203252
更新日期:2000-01-06 00:00:00
abstract::Initiation of DNA replication requires the function of MCM gene products, which participate in ensuring that DNA replication occurs only once in the cell cycle. Expression of all mammalian genes of the MCM family is induced by growth stimulation, unlike yeast, and the mRNA levels peak at G1/S boundary. In this study, ...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1202544
更新日期:1999-04-08 00:00:00
abstract::The p53 transcription factor has a critical role in cell stress response and in tumor suppression. Wild-type p53 protein is a growth modulator and its inactivation is a critical event in malignant transformation. It has been recently demonstrated that wild-type p53 has developmental and differentiation functions. Inde...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2011.31
更新日期:2011-07-07 00:00:00
abstract::We previously described the isolation of non-tumorigenic revertants from mutagenized populations of v-fos-transformed Rat-1 cells (Zarbl et al., 1987). In the present study we examined the possibility that the revertant phenotype resulted from mutations that altered the expression or activities of the c-jun or junB pr...
journal_title:Oncogene
pub_type: 杂志文章
doi:
更新日期:1994-10-01 00:00:00
abstract::Polyoma small T antigen (PyST), an early gene product of the polyoma virus, has been shown to cause cell death in a number of mammalian cells in a protein phosphatase 2A (PP2A)-dependent manner. In the current study, using a cell line featuring regulated expression of PyST, we found that PyST arrests cells in mitosis....
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2014.192
更新日期:2015-05-07 00:00:00
abstract::Neogenin is a member of the N-CAM family of cell adhesion molecules and is closely related to the DCC tumor suppressor gene product. Recently, it has been demonstrated that the DCC/Neogenin subfamily plays a key role in axonal guidance within the embryonic nervous system, however little is known about the function of ...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1201225
更新日期:1997-08-07 00:00:00
abstract::The Neuregulins and their receptors, the ErbB/HER subfamily of receptor tyrosine kinases, have critical roles in animal physiology, and their deregulation is frequent in cancer. Here we report the identification of the guanine nucleotide exchange factor, phosphatidylinositol 3,4,5-triphosphate-dependent Rac exchanger ...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2010.489
更新日期:2011-03-03 00:00:00
abstract::In contrast to other cell cycle inhibitors, the tumor suppressor p16Ink4a is not detectable or expressed at very low levels in embryonic and adult mouse tissues, and therefore it has often been considered as a specialized checkpoint protein that does not participate in the control of normal cell cycle progression. How...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1209437
更新日期:2006-07-06 00:00:00
abstract::Transcription from the rat transforming growth factor alpha (TGF-alpha) promoter initiates at multiple sites within a 200-bp G+C-rich region that lacks TATA and CAAT motifs but contains multiple potential binding sites for the transcription factor Sp1. In the present study, we used deletion analysis to establish the 5...
journal_title:Oncogene
pub_type: 杂志文章
doi:
更新日期:1992-09-01 00:00:00
abstract::CD97, a member of the adhesion family of G-protein-coupled receptors (GPCRs), complexes with and potentiates lysophosphatidic acid (LPA) receptor signaling to the downstream effector RHOA. We show here that CD97 was expressed in a majority of thyroid cancers but not normal thyroid epithelium and that the level of CD97...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2012.301
更新日期:2013-05-30 00:00:00
abstract::The marine alkaloid ascididemin (ASC) was shown to exert cytotoxicity even against multidrug-resistant cancer cells. Here, we address the signaling pathways utilized by ASC to trigger apoptosis in Jurkat leukemia T cells. We show that ASC (0.5-20 microM) induces a mitochondrial pathway that requires the activation of ...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1207281
更新日期:2004-02-26 00:00:00
abstract::Although ErbB2 is known to enhance breast cancer metastasis, the signaling events responsible for this remain elusive. Alpha-isozyme of protein kinase C (PKCalpha), which is involved in cancer development and progression, has been suggested to be activated by ErbB2 without direct evidence. In addition, the roles of PK...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1209361
更新日期:2006-06-01 00:00:00
abstract::ErbB-2 is an orphan receptor that belongs to a family of tyrosine kinase receptors for either epidermal growth factor (EGF) or Neu differentiation factor (NDF/neuregulin). Because overexpression of the erbB-2 proto-oncogene is frequently associated with an aggressive clinical course of certain human adenocarcinomas, t...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1201029
更新日期:1997-05-01 00:00:00
abstract::p53 is known to play a role in iron homeostasis and is required for FDXR-mediated iron metabolism via iron regulatory protein 2 (IRP2). Interestingly, p53 is frequently mutated in tumors wherein iron is often accumulated, suggesting that mutant p53 may exert its gain of function by altering iron metabolism. In this st...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/s41388-019-0876-5
更新日期:2019-08-01 00:00:00