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: the extreme amino-terminal region, a domain which binds p105Rb family members, and the bipartite p53-binding region. Many studies have attempted to define the activities and regions of SV40 large T antigen required for immortalization of mouse embryo fibroblasts (MEFs). In most of these studies, investigators have used survival of T antigen-expressing primary MEF colonies at the time when controls MEFs undergo senescence as a measurement of 'immortalization' and concluded that immortalization of MEFs is correlated with large T antigen's ability to sequester the human tumor suppressor gene product p53 and separable from its p105Rb-binding or N terminal functions. In order to more rigorously define the regions of SV40 large T antigen required for escape from senescence, individual T antigen-expressing primary MEF colonies were systematically subcultured for > 60 population doublings beyond the time of control MEF senescence under conditions known to limit the number of spontaneously immortalized cells. We found that although interaction of T antigen with p53 was sufficient to substantially extend the lifespan of MEFs, all three SV40 large T antigen domains required for REF 52 transformation were necessary to immortalize primary MEFs. These results indicate that p53 inactivation alone is insufficient to immortalize primary MEFs; rather, immortalization requires multiple activities of T antigen which are also required for efficient transformation.
journal_name
Oncogenejournal_title
Oncogeneauthors
Conzen SD,Cole CNsubject
Has Abstractpub_date
1995-12-07 00:00:00pages
2295-302issue
11eissn
0950-9232issn
1476-5594journal_volume
11pub_type
杂志文章相关文献
ONCOGENE文献大全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::In this age of targeted therapy, identification of molecular pathways that are deregulated in cancer will not only elucidate underlying tumorigenic mechanisms, but may also help to determine the classes of drugs that are used for treatment. In kidney cancer, a spectrum of histological subtypes exists that are characte...
journal_title:Oncogene
pub_type: 杂志文章,评审
doi:10.1038/sj.onc.1210256
更新日期:2007-02-26 00:00:00
abstract::Apoptin has been described to induce apoptosis in various human cancer cell lines, but not in normal cells, thus making it an interesting candidate for the development of novel therapeutic strategies. Apoptin was generated and cloned into several mammalian expression vectors. Transfection or microinjection of apoptin ...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1207224
更新日期:2004-02-05 00:00:00
abstract::The REL gene is amplified in many human B-cell lymphomas and we have previously shown that expression of REL from a retroviral vector can malignantly transform chicken spleen cells in vitro. To identify REL protein functions necessary for malignant transformation, we have performed deletion analysis on REL sequences e...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1206801
更新日期:2003-10-09 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::The activities of E2F transcription factors are inhibited by interactions with members of the retinoblastoma (RB) tumor suppressor family, p105RB, p107 and p130. In cycling cells p107 and p130 also interact with heterodimers comprised of Cdk2 and either A or E cyclins. We characterized E2F complexes present in C2C12 a...
journal_title:Oncogene
pub_type: 杂志文章
doi:
更新日期:1995-09-07 00:00:00
abstract::Recently, the MLL gene at 11q23 was found to be involved in a subset of leukemias with an 11q23 abnormality. In the present study, we isolated chimeric cDNAs between the MLL and a gene designated MLLT3 at 9p22 from a cDNA library of an IMS-M1 cell line with a t(9;11)(p22;q23) translocation, a representative karyotypic...
journal_title:Oncogene
pub_type: 杂志文章
doi:
更新日期:1993-11-01 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::Expression microarray analysis identified CITED1 among a group of genes specifically upregulated in the pubertal mouse mammary gland. At puberty, CITED1 localizes to the luminal epithelial cell population of the mammary ducts and the body cells of the terminal end buds. Generation of CITED1 gene knockout mice showed t...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1209183
更新日期:2006-03-09 00:00:00
abstract::The Epstein-Barr virus (EBV) encoded Latent Membrane Protein-1 (LMP1) mimics a constitutively active receptor molecule, and has been shown to activate NF-kappaB and the MAPK and JNK pathways. Two regions within the cytosolic domain of LMP1 have been found to effect cell signalling. One of these, the carboxy-terminal a...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1202144
更新日期:1998-11-05 00:00:00
abstract::While 25% of human cancers harbor oncogenic Ras mutations, such mutations are not found in astrocytomas. We have previously demonstrated that the activation of receptor tyrosine kinases expressed by malignant human astrocytoma cells and specimens results in functional upregulation of the Ras signalling pathway and inc...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1203105
更新日期:1999-12-09 00:00:00
abstract::In spite of relentless efforts to devise new treatment strategies, primary glioblastomas invariably recur as aggressive, therapy-resistant relapses and patients rapidly succumb to these tumors. Many therapeutic agents are first tested in clinical trials involving recurrent glioblastomas. Remarkably, however, fundament...
journal_title:Oncogene
pub_type: 杂志文章,评审
doi:10.1038/onc.2016.85
更新日期:2016-11-10 00:00:00
abstract::Epigenetic regulation of gene expression is critical in the maintenance of cellular homeostasis. Dysregulation of normal epigenetic transcription occurs in abnormal physiological conditions, such as those seen in cancer cells and cells infected with parasites, making the mechanism underlying abnormal epigenetic transc...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1208394
更新日期:2005-03-10 00:00:00
abstract::14-3-3sigma proteins regulate numerous cellular processes that are important to cancer development. One of its biological roles involves G2 cell-cycle arrest following DNA damage. It has also been reported that the loss of 14-3-3sigma expression via CpG methylation may contribute to malignant transformation by impairi...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1209462
更新日期:2006-08-03 00:00:00
abstract::The Rb protein is a tumor suppressor, which plays a pivotal role in the negative control of the cell cycle and in tumor progression. It has been shown that Rb protein (pRb) is responsible for a major G1 checkpoint, blocking S-phase entry and cell growth. The retinoblastoma family includes three members, Rb/p105, p107 ...
journal_title:Oncogene
pub_type: 杂志文章,评审
doi:10.1038/sj.onc.1209615
更新日期:2006-08-28 00:00:00
abstract::The DNA-binding, transcriptional activation and transforming activities of the Myc protein require dimerization with Max. Max can form also homodimers which are able to bind the same DNA sequence as Myc/Max heterodimers and suppress Myc-induced transcription and transformation. We have recently identified a naturally ...
journal_title:Oncogene
pub_type: 杂志文章
doi:
更新日期:1995-08-03 00:00:00
abstract::Increased glucose consumption is a hallmark of cancer cells. The increased consumption and subsequent metabolism of glucose during proliferation creates the need for a constant supply of NAD, a co-factor in glycolysis. Regeneration of the NAD required to support enhanced glycolysis has been attributed to the terminal ...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2017.36
更新日期:2017-07-06 00:00:00
abstract::MicroRNAs (miRNAs) have important roles in the initiation and progression of human cancer, but their role in head and neck cancer development and progression is not well defined. We aimed to determine whether specific miRNAs and their target mRNAs contribute to head and neck cancer pathogenesis and progression. To ide...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2013.13
更新日期:2014-02-06 00:00:00
abstract::Waldenström macroglobulinemia (WM) is a proliferative disorder of IgM-secreting, lymphoplasmacytoid cells that inhabit the lymph nodes and bone marrow. The disease carries a high prevalence of activating mutations in MyD88 (91%) and CXCR4 (28%). Because signaling through these pathways leads to Bcl-xL induction, we ex...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2015.103
更新日期:2016-01-28 00:00:00
abstract::Tyrosine kinase receptors have an essential role in various aspects of tumor progression. In particular, epidermal growth factor receptor (EGFR) and its ligands have been implicated in the growth and dissemination of a wide array of human carcinomas. Here, we describe an EGFR-mediated signaling pathway that regulates ...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2011.450
更新日期:2012-05-31 00:00:00
abstract::SH3 and SAM domains are protein interaction motifs that are predominantly seen in signaling molecules, adaptors, and scaffold proteins. We have identified a novel family of putative adaptor genes that includes HACS1. HACS1 encodes a 441 amino acid protein that is differentially expressed in hematopoietic cells and has...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1204698
更新日期:2001-08-30 00:00:00
abstract::Friend virus-induced erythroleukemia involves two members of the ETS family of transcriptional regulators, both activated via proviral insertion in the corresponding loci. Spi-1/PU.1 is expressed in the disease induced by the original Friend virus SFFV(F-MuLV) complex in adult mice. In contrast, FLI-1 is overexpressed...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1202534
更新日期:1999-02-25 00:00:00
abstract::Epstein-Barr virus (EBV) latent membrane protein 1 (LMP1) has been suggested to be involved in tumor metastasis. However, the molecular mechanism of LMP1-induced metastasis is largely unknown. In this study, we investigated the effect of LMP1 on the expression of RECK, a metastasis suppressor gene, in an EBV-negative ...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1207157
更新日期:2003-11-13 00:00:00
abstract::The MAP kinase pathway impinging on ERK2 has been shown to be integrally associated with mitogenic signalling in many cell types. Previously, we and others have demonstrated that oncogenic forms of Raf-1 kinase, when expressed in fibroblasts, lead to the constitutive activation of ERK2, the de-regulation of c-fos expr...
journal_title:Oncogene
pub_type: 杂志文章
doi:
更新日期:1995-11-16 00:00:00
abstract::A mutation in codon 122 of the mouse p53 gene resulting in a T to L amino acid substitution (T122-->L) is frequently associated with skin cancer in UV-irradiated mice that are both homozygous mutant for the nucleotide excision repair (NER) gene Xpc (Xpc(-/-)) and hemizygous mutant for the p53 gene. We investigated the...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1205779
更新日期:2002-08-22 00:00:00
abstract::The E2F1 transcription factor, which is deregulated in most human cancers by mutations in the p16-cyclin D-Rb pathway, has both oncogenic and tumor-suppressive properties. This is dramatically illustrated by the phenotype of an E2F1 transgenic mouse model that spontaneously develops tumors in the skin and other epithe...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1209120
更新日期:2006-02-09 00:00:00
abstract::Bone metastatic prostate cancer provokes extensive osteogenesis by driving the recruitment and osteoblastic differentiation of mesenchymal stromal cells (MSCs). The resulting lesions greatly contribute to patient morbidity and mortality, underscoring the need for defining how prostate metastases subvert the MSC-osteob...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/s41388-019-0913-4
更新日期:2019-10-01 00:00:00
abstract::Gene silencing associated with aberrant methylation of promoter region CpG islands is one mechanism in which tumor suppressor genes are inactivated in human cancers. Recently, we identified a novel gene, Target of Methylation-associated Silencing-1 (TMS1) (also called ASC), which is aberrantly methylated and silenced ...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1206430
更新日期:2003-05-29 00:00:00
abstract::There is strong evidence at the individual level and the population level that an efficient cytotoxic T lymphocyte (CTL) response to HTLV-1 limits the proviral load and the risk of associated inflammatory diseases such as HAM/TSP. This evidence comes from host population genetics, viral genetics, DNA expression microa...
journal_title:Oncogene
pub_type: 杂志文章,评审
doi:10.1038/sj.onc.1208970
更新日期:2005-09-05 00:00:00
abstract::A growing body of literature suggests that the ubiquitously expressed Src family kinases (Src, Fyn and Yes) are required for agents such as platelet-derived growth factor (PDGF) to stimulate DNA synthesis. Yet Klinghoffer and colleagues recently presented evidence that fibroblasts derived from mice null for Src, Fyn a...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1203608
更新日期:2000-06-01 00:00:00