Abstract:
:Rhabdomyosarcoma (RMS) tumors are the most common soft-tissue sarcomas in childhood. In this investigation, we show that myostatin, a skeletal muscle-specific inhibitor of growth and differentiation is expressed and translated in the cultured RMS cell line, RD. The addition of exogenous recombinant myostatin inhibits the proliferation of RD cells cultured in growth media, consistent with the role of myostatin in normal myoblast proliferation inhibition. However, unlike normal myoblasts, upregulation of p21 was not observed. Rather, myostatin signalling resulted in the specific downregulation of both Cdk2 and its cognate partner, cyclin-E. The analysis of Rb reveals that there was no change in its phosphorylation status with myostatin treatment, consistent with D-type-cyclin-Cdk4/6 complexes being active in the absence of p21. Moreover, the activity of Rb appeared to be unchanged between treated and nontreated RD cells, as determined by the ability of Rb to bind E2F1. The examination of NPAT, a substrate of cyclin-E-Cdk2 involved in the transcriptional activation of replication-dependent histone gene expression, revealed that it undergoes a loss of phosphorylation with myostatin treatment. Supporting this, a downregulation in H4-histone gene expression was observed. These results suggest that myostatin could potentially be used as an inhibitor of RMS proliferation and define a previously uncharacterized, Rb-independent mechanism for the inhibition of muscle precursor cell proliferation by myostatin.
journal_name
Oncogenejournal_title
Oncogeneauthors
Langley B,Thomas M,McFarlane C,Gilmour S,Sharma M,Kambadur Rdoi
10.1038/sj.onc.1207144subject
Has Abstractpub_date
2004-01-15 00:00:00pages
524-34issue
2eissn
0950-9232issn
1476-5594pii
1207144journal_volume
23pub_type
杂志文章相关文献
ONCOGENE文献大全abstract::UV irradiation of mammalian cells results in the activation of transcription factors which mediate induction of early response genes designed to repair and minimise the damage sustained by the cell. Evidence from studies in HeLa cells suggest that UVC regulates NF-kappa B activity via tyrosine kinases and activation o...
journal_title:Oncogene
pub_type: 杂志文章
doi:
更新日期:1996-02-15 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::Adenomatous polyposis coli (APC) gene mutations have been implicated in familial and sporadic gastrointestinal (GI) cancers. APC mutations are associated with autosomal dominant inheritance of disease in humans. Similarly, mice that contain a single mutant APC gene encoding a protein truncated at residue 716 (Apc(Δ716...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2010.633
更新日期:2011-06-09 00:00:00
abstract::The cancer chemopreventive synthetic retinoid N-(4-hydroxyphenyl)retinamide (HPR) can inhibit the growth and induce apoptosis of tumor cells. In this study we analysed the growth suppressive effect of HPR on human breast cancer cell lines in vitro and the role of the retinoblastoma protein (pRb) in this response. Trea...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1203743
更新日期:2000-08-17 00:00:00
abstract::Bloom's syndrome (BS) arises through mutations in both copies of the BLM gene that encodes a RecQ 3'-5' DNA helicase. BS patients are predisposed to developing all the cancers that affect the general population, and BS cells exhibit marked genetic instability. We showed recently that BLM protein contributes to the cel...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1205246
更新日期:2002-03-27 00:00:00
abstract::Polyoma virus (Py) differs from other small DNA tumor viruses in not encoding a protein that inactivates p53. The complete Py early region encoding the large T-antigen (PyLT), middle T-antigen (PyMT) and small T-antigen (PyST) will transform primary rodent cells and REF52 cells, but PyMT, the main Py oncogene, by itse...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1204717
更新日期:2001-08-16 00:00:00
abstract::Shb is a recently described Src homology 2 (SH2) domain-containing adaptor protein. Here we show that Shb is expressed in lymphoid tissues, and is recruited into signaling complexes upon activation of Jurkat T cells. Grb2 binds proline-rich motifs in Shb via its SH3 domains. As a result, a number of proteins detected ...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1201607
更新日期:1998-02-19 00:00:00
abstract::The BCL6 gene, mapped at the chromosomal band 3q27, encodes a POZ/Zinc finger transcription repressor protein. It is frequently activated in Non-Hodgkin's lymphomas (NHL) by translocations with breakpoints clustering in the 5' major breakpoint region (MBR) as well as by mutations in the same region. The translocations...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1202098
更新日期:1998-10-01 00:00:00
abstract::We have previously reported on the identification of a cDNA (placenta growth factor, PlGF) coding for a novel angiogenic factor expressed in placental tissue that is similar to vascular permeability factor/vascular endothelial growth factor (VPF/VEGF). Biochemical and functional characterization of PlGF derived from t...
journal_title:Oncogene
pub_type: 杂志文章
doi:
更新日期:1993-04-01 00:00:00
abstract::The chromatin state is finely tuned to regulate function and specificity for transcription factors such as oestrogen receptor alpha (ER), which contributes to cell growth in breast cancer. ER transcriptional potential is mediated, in large part, by the specific associated proteins and co-factors that interact with it....
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/s41388-018-0312-2
更新日期:2018-09-01 00:00:00
abstract::Ras-genes encode for proteins important for transmitting extracellular signals from the cytoplasm to the nucleus. In this study we investigated the impact of Ras on cell cycle progression after hepatectomy by using adenoviral vectors (adv) expressing beta-galactosidase (beta-gal), a dominant-negative (Ras N17) or a do...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1204690
更新日期:2001-08-30 00:00:00
abstract::We previously showed that the proto-oncogene RON encodes the tyrosine kinase receptor for Macrophage Stimulating Protein (MSP), originally isolated as a chemotactic factor for peritoneal macrophages. To elucidate the biological role of MSP we studied the expression of the Ron receptor in vivo, and the response to the ...
journal_title:Oncogene
pub_type: 杂志文章
doi:
更新日期:1995-12-21 00:00:00
abstract::Human xeroderma pigmentosum (XP) fibroblasts were transformed with N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). The transformed cells, called ASKMN, were immortalized, grew in agar and were tumorigenic in nude mice. A trp-met oncogene was identified in ASKMN cells, after transfection of high molecular weight DNA on 3T...
journal_title:Oncogene
pub_type: 杂志文章
doi:
更新日期:1993-07-01 00:00:00
abstract::Functional alterations or loss of tumor-suppressor genes are an important feature of neoplastic progression in humans. The employment of suitable animal model systems would greatly facilitate the detection and manipulation of such genes. We describe here an experimental approach to this problem based on the analysis o...
journal_title:Oncogene
pub_type: 杂志文章
doi:
更新日期:1991-12-01 00:00:00
abstract::Polo-like kinases play critical roles during multiple stages of cell cycle progression. All Polo-like kinases contain an N-terminal Ser/Thr kinase catalytic domain and a C-terminal region that contains one or two Polo-boxes. For Polo-like kinase 1, 2, and 3, and their homologs, the entire C-terminal region, including ...
journal_title:Oncogene
pub_type: 杂志文章,评审
doi:10.1038/sj.onc.1208280
更新日期:2005-01-10 00:00:00
abstract::A key hallmark of many cancers, particularly the most aggressive, is the capacity to metabolize glucose at an elevated rate, a phenotype detected clinically using positron emission tomography (PET). This phenotype provides cancer cells, including those that participate in metastasis, a distinct competitive edge over n...
journal_title:Oncogene
pub_type: 杂志文章,评审
doi:10.1038/sj.onc.1209603
更新日期:2006-08-07 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::Vascular endothelial (VE)-cadherin is exclusively expressed at interendothelial junctions of normal and tumour vessels. In this report, we characterized the transcriptional activity of the human VE-cadherin promoter. Transient transfection assays revealed that sequences at positions --1135/-744 and -166/-5 base pairs ...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1208483
更新日期:2005-04-21 00:00:00
abstract::Epigenetic regulations play crucial roles in leukemogenesis and leukemia progression. SUV39H1 is the dominant H3K9 methyltransferase in the hematopoietic system, and its expression declines with aging. However, the role of SUV39H1 via its-mediated repressive modification H3K9me3 in leukemogenesis/leukemia progression ...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/s41388-020-01495-6
更新日期:2020-12-01 00:00:00
abstract::The transcription factor Cdx1 regulates intestine-specific gene expression and enterocyte differentiation. It has been hypothesized to play a role in regulating intestinal cell proliferation; however, the mechanism for this effect remains elusive. In a prior study, we demonstrated that Cdx1 expression reduced the prol...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1206770
更新日期:2003-09-25 00:00:00
abstract::Liver tumor-initiating cells (TICs), the drivers for liver tumorigenesis, accounts for liver tumor initiation, metastasis, drug resistance and relapse. Wnt/β-catenin signaling pathway emerges as a critical modulator in liver TIC self-renewal. However, the molecular mechanism of Wnt/β-catenin initiation in liver tumori...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/s41388-018-0203-6
更新日期:2018-06-01 00:00:00
abstract::Cell to cell communication is vital throughout the development of multicellular organisms and during adult homeostasis. One way in which communication is achieved is through the secretion of signaling molecules that are received by neighboring responding cells. Wnt ligands comprise a large family of secreted, hydropho...
journal_title:Oncogene
pub_type: 杂志文章,评审
doi:10.1038/sj.onc.1210053
更新日期:2006-12-04 00:00:00
abstract::Mxi1 is a basic region helix-loop-helix leucine zipper (bHLH/LZ) protein that, in association with Max, antagonizes Myc oncogenic activities. A possible mechanistic basis for Mxi1-mediated repression was provided by the recent demonstration that the repressive potential of Mxi1 correlates with its ability to physicall...
journal_title:Oncogene
pub_type: 杂志文章
doi:
更新日期:1996-03-07 00:00:00
abstract::Hepatocellular carcinoma (HCC) metastasis is largely responsible for HCC-associated recurrence and mortality. We aimed to identify metastasis-related long non-coding RNAs (lncRNAs) to understand the molecular mechanism of HCC metastasis. We first identified that miR-1258 was downregulated in HCC tissues both in The Ca...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/s41388-020-1307-3
更新日期:2020-06-01 00:00:00
abstract::The MET oncogene encodes the receptor for HGF/Scatter Factor, known to control cell motility and invasion in epithelial cells. We report that the Met/HGF receptor, absent in differentiated adult skeletal muscles, is aberrantly expressed in clinical samples and in established cell lines of human rhadbomyosarcomas. In b...
journal_title:Oncogene
pub_type: 杂志文章
doi:
更新日期:1996-04-18 00:00:00
abstract::PI3K/AKT pathway activation is thought to be a driving force in metastatic melanomas. Members of the pleckstrin homology (PH) domain leucine-rich repeat protein Ser/Thr specific phosphatase family (PHLPP1 and PHLPP2) can regulate AKT activation. By dephosphorylating specific serine residues in the hydrophobic motif, P...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/s41388-017-0061-7
更新日期:2018-04-01 00:00:00
abstract::RING-finger proteins play crucial roles in ubiquitination events involved in diverse cellular processes including signal transduction, differentiation and apoptosis. Most of the RING-finger proteins have E3-ubiquitin ligase activity. RNF11 is a small RING-finger protein and harbors a RING-H2 domain and a PY motif that...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1207319
更新日期:2004-03-11 00:00:00
abstract::Constitutive activation of the signal transducer and activator of transcription 3 (Stat3) and mutation of the p53 are both commonly detected in human prostate cancer cells. We sought to investigate whether there is functional regulation of Stat3 by wild-type (wt) p53. Our results demonstrate that expression of wt p53 ...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1205426
更新日期:2002-05-02 00:00:00
abstract::Signal transducer and activator of transcription 3 (STAT3) is constitutively activated in malignant tumors and plays important roles in multiple aspects of cancer aggressiveness. Thus, targeting STAT3 promises to be an attractive strategy for the treatment of advanced metastatic tumors. Bisindolylmaleimide alkaloid (B...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/s41388-017-0076-0
更新日期:2018-05-01 00:00:00
abstract::DNA damage response (DDR), the guardian of genomic integrity, emerges as an oncogene-inducible biological barrier against progression of cancer beyond its early stages. Recent evidence from both cell culture and animal models as well as analyses of clinical specimens show that activation of numerous oncogenes and loss...
journal_title:Oncogene
pub_type: 杂志文章,评审
doi:10.1038/sj.onc.1210881
更新日期:2007-12-10 00:00:00