Abstract:
:RasGRP1 is a Ras-specific exchange factor, which is activated by T-cell receptor (TCR) and promotes TCR-dependent positive selection of thymocytes. RasGRP1 is highly expressed on most T lymphocytic leukemias and is a common site of proviral insertion in retrovirus-induced murine T-cell lymphomas. We used RasGRP1 transgenic mice to determine if deregulated expression of RasGRP1 has a causative role in the development of T-cell malignancies. Thymic lymphomas occurred in three different RasGRP1 transgenic mouse lines. Thymocyte transformation correlated with high transgene expression in early stage lymphomas, indicating that deregulated RasGRP1 expression contributed to the initiation of lymphomagenesis. Expression of the positively selectable H-Y TCR accelerated lymphomagenesis in RasGRP1 transgenic mice. However, the transformed thymocytes lacked markers of positive selection and lymphomas occurred when positive selection was precluded by negative selection of the H-Y TCR. Therefore, initiation of lymphomagenesis via RasGRP1 was not associated with TCR-dependent positive selection of thymocytes. Thymic lymphomas occurred in RasGRP1 transgenic/Rag2-/- mice, demonstrating that neither TCR nor pre-TCR were required for RasGRP1-driven lymphomagenesis. The RasGRP1 transgene conferred pre-TCR-independent survival and proliferation of immature thymocytes, suggesting that deregulated expression of RasGRP1 promotes lymphomagenesis by expanding the pool of thymocytes which are susceptible to transformation.
journal_name
Oncogenejournal_title
Oncogeneauthors
Klinger MB,Guilbault B,Goulding RE,Kay RJdoi
10.1038/sj.onc.1208334subject
Has Abstractpub_date
2005-04-14 00:00:00pages
2695-704issue
16eissn
0950-9232issn
1476-5594pii
1208334journal_volume
24pub_type
杂志文章相关文献
ONCOGENE文献大全abstract::The diverse checkpoint responses to DNA damage may reflect differential sensitivities by molecular components of the damage-signalling network to the type and amount of lesions. Here, we determined the kinetics of activation of the checkpoint kinases ATM and Chk2 (the latter substrate of ATM) in relation to the initia...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1207986
更新日期:2004-10-07 00:00:00
abstract::Colony-stimulating factors and other cytokines signal via their cognate receptors to regulate hematopoiesis. In many developmental systems, inductive signalling determines cell fate and, by analogy with this, it has been postulated that cytokines, signalling via their cognate receptors, may play an instructive role in...
journal_title:Oncogene
pub_type: 杂志文章,评审
doi:10.1038/sj.onc.1210756
更新日期:2007-10-15 00:00:00
abstract::Expression of oncogenic H-Ras in 23A2 myoblasts (A2:H-Ras cells) is sufficient to induce both a transformed phenotype and a differentiation-defective phenotype. Because oncogenic Ras is known to induce the secretion of several different growth factors involved in maintaining the transformed phenotype of both fibroblas...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1201423
更新日期:1997-11-20 00:00:00
abstract::The chicken c-ets-1 locus encodes two transcription factors, p54c-ets-1 and p68c-ets-1 that differ in their N-termini, encoded respectively by the I54 and alpha beta exons. p68c-ets-1 equivalents are only found in birds and reptiles while p54c-ets-1 is widely conserved in vertebrates, from amphibians to mammals. Thus,...
journal_title:Oncogene
pub_type: 杂志文章
doi:
更新日期:1994-11-01 00:00:00
abstract::We have determined the genomic structure of the mouse fra-1 gene, which consists of four exons and three introns at positions also found in the other members of the fos gene family. Fra-1 is expressed rather highly in the brain and testes of adult mice, and at low levels in most other tissues. Absence of c-Fos leads t...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1201460
更新日期:1997-09-04 00:00:00
abstract::Mcl-1 is an antiapoptotic member of the Bcl-2 family that can promote cell viability. We report here that Mcl-1 is a new substrate for caspases during induction of apoptosis. Mcl-1 cleavage occurs after Asp127 and Asp157 and generates four fragments of 24, 19, 17 and 12 kDa in both intact cells and in vitro, an effect...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1208069
更新日期:2004-10-14 00:00:00
abstract::Activation of the p53 tumor suppressor protein can lead to either cell cycle arrest or apoptosis. Several functional domains necessary for mediating cell cycle arrest and apoptosis in p53 have been mapped, e.g., the proline-rich domain. The proline-rich domain is located within residues 60-90, which comprise five PXXP...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1202533
更新日期:1999-03-25 00:00:00
abstract::Anaplastic lymphoma kinase (ALK) is a receptor tyrosine kinase aberrantly expressed in neuroblastoma, a devastating pediatric cancer of the sympathetic nervous system. Germline and somatically acquired ALK aberrations induce increased autophosphorylation, constitutive ALK activation and increased downstream signaling....
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2011.647
更新日期:2012-11-15 00:00:00
abstract::The BTB/POZ family of proteins has been implicated in multiple biological processes, including tumourigenesis, DNA damage responses and cell cycle progression and development. MIZ-1 (Myc-interacting zinc-finger protein 1) is known to activate transcription of CDKN1A. We recently found that a kidney cancer-related POK ...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2011.331
更新日期:2012-03-15 00:00:00
abstract::Medulloblastoma (MB) is the most common malignant pediatric brain tumor. Since surviving patients experience severe neurocognitive disabilities, better and more effective treatments are needed to enhance their quality of life. Casein kinase 2 (CK2) is known to regulate cell growth and survival in multiple cancers; how...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/s41388-019-0927-y
更新日期:2019-10-01 00:00:00
abstract::Delta(9)-Tetrahydrocannabinol (THC) is the primary cannabinoid of marijuana and has been shown to either potentiate or inhibit tumor growth, depending on the type of cancer and its pathogenesis. Little is known about the activity of cannabinoids like THC on epidermal growth factor receptor-overexpressing lung cancers,...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1210641
更新日期:2008-01-10 00:00:00
abstract::Growth arrest after u.v. damage was investigated in C3H mouse primary cultured hepatocytes, spontaneously immortalized liver epithelial cells and their H-ras-transformed derivatives. All cells except for one of the transformed lines had the wild type p53 gene considered necessary for the G1-S checkpoint. Growth arrest...
journal_title:Oncogene
pub_type: 杂志文章
doi:
更新日期:1994-10-01 00:00:00
abstract::Wnt signaling plays an important role in embryonic development and tumorigenesis. These biological effects are exerted by activation of the beta-catenin/TCF transcription complex and consequent regulation of a set of downstream genes. TCF-binding elements have been found in the promoter regions of many TCF target gene...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1207892
更新日期:2004-11-04 00:00:00
abstract::Ras proteins activate Raf and PI-3 kinases, as well as exchange factors for RalA and RalB GTPases. Many previous studies have reported that the Ral-signaling cascade contributes positively to Ras-mediated oncogenesis. Here, using a bioengineered tissue model of early steps in Ras-induced human squamous cell carcinoma ...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2009.307
更新日期:2010-01-07 00:00:00
abstract::Lymphoblastoid cell lines derived from cancer prone Bloom's Syndrome patients differ from cell lines representative of several other disorders by exhibiting a constitutive elevation in the level of the c-myc protein. This may be a contributing factor in the strong predisposition to malignancy observed in Bloom's syndr...
journal_title:Oncogene
pub_type: 杂志文章
doi:
更新日期:1989-12-01 00:00:00
abstract::Simian virus 40 (SV40) is a small DNA tumor virus whose early region gene product, large T antigen, is sufficient to immortalize primary rodent cells and transform established rodent cell lines. Three functional domains of large T antigen are required for transformation of the rat embryo fibroblast REF 52 cell line: t...
journal_title:Oncogene
pub_type: 杂志文章
doi:
更新日期:1995-12-07 00:00:00
abstract::Ovarian cancer is the leading cause of death among all gynecological malignancies due to the development of acquired chemoresistance and disease relapse. Although the role of cancer stem cells (CSCs), a subset of tumor cells with the self-renewal and differentiation capabilities, in therapeutic resistance is beginning...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2016.320
更新日期:2017-03-01 00:00:00
abstract::The Wilms' tumor suppressor gene, WT1, functions as a transcriptional regulator that represses or activates the expression of a variety of putative target genes. However, it is not clear which genes are the biological targets of WT1, nor which cellular pathway(s) is critically altered in tumors as a result of WT1 muta...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1206597
更新日期:2003-06-12 00:00:00
abstract::Gene expression patterns in normal and v-myc-transformed quail embryo fibroblasts were compared by mRNA differential display. Displaying approximately 2500 mRNA species by reverse transcription/PCR, reamplification of 73 differential cDNA fragments and rescreening by Northern analysis led to the isolation of a clone, ...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1200930
更新日期:1997-03-06 00:00:00
abstract::Mel-18 has been implicated in several processes in tumor progression, in which the Akt pathway is involved as an important key molecular event. However, the function of Mel-18 in human cancers has not been fully established yet. Here, we examined the effect of Mel-18 on tumor angiogenesis in human breast cancer, and f...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2011.174
更新日期:2011-11-10 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::Junctional adhesion molecule-A (JAM-A) is a membranous cell-cell adhesion protein involved in tight-junction formation in epithelial and endothelial cells. Its overexpression in breast tumors has recently been linked with increased risk of metastasis. We sought to identify if JAM-A overexpression was associated with s...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2012.276
更新日期:2013-05-30 00:00:00
abstract::Mechanisms underlying multidrug resistance (MDR), one of the major causes of cancer treatment failure, are still poorly understood. We selected the osteosarcoma MDR HosDXR150 cell line by culturing Hos cells in the presence of increasing doxorubicin doses and showed that it is crossresistant to vinblastine. Similarly ...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1206487
更新日期:2003-06-05 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::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 c-erbB-2 proto-oncogene encodes a receptor tyrosine kinase (RTK) closely related to the epidermal growth factor receptor (EGFR). Overexpression of erbB-2 occurs in approximately 20% of human breast tumours, where increased expression correlates with poor patient prognosis. The EGFR is coupled to the Ras signalling...
journal_title:Oncogene
pub_type: 杂志文章
doi:
更新日期:1994-12-01 00:00:00
abstract::The phosphatidylinositol 3-kinase (PI3K)/AKT and RAS oncogenic signalling modules are frequently mutated in sporadic human cancer. Although each of these pathways has been shown to play critical roles in driving tumour growth and proliferation, their activation in normal human cells can also promote cell senescence. A...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2011.394
更新日期:2012-04-12 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::We have identified a novel mechanism of cross-talk between cell signaling and metabolic pathways, whereby the signaling kinase p21-activated kinase 1 (Pak1) binds to, phosphorylates and enhances the enzymatic activity of phosphoglucomutase 1 (PGM), an important regulatory enzyme in cellular glucose utilization and ene...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1207969
更新日期:2004-10-21 00:00:00
abstract::As apoptosis defects limit efficacy of anticancer agents, autophagy has been proposed as a novel strategy for radiotherapy enhancement. We previously showed that caspase-3/7 inhibition induces autophagy and promotes radiosensitivity in vitro and in vivo. Therefore, we further investigated the mechanism by which radiat...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2010.74
更新日期:2010-06-03 00:00:00