Abstract:
:Ataxia telangiectasia (AT) is a human hereditary syndrome whose underlying gene product, ataxia telangiectasia mutated (ATM) protein kinase, is involved in multiple intracellular signaling pathways. We demonstrated previously that AT fibroblasts are defective in intracellular Ca(2+) mobilization in response to both stress-inducing and mitogenic stimuli. To extend these findings, normal and AT cells were exposed to serum in the presence of different concentrations of extracellular Ca(2+) ([Ca(2+)](o)), and release of intracellular Ca(2+), activation of calmodulin-dependent protein kinase II and phosphorylation of kinases ERK1 and 2 were monitored. When maintained in high [Ca(2+)](o) (0.42 mM), normal fibroblasts responded to serum introduction more rapidly and efficiently than did AT cells. Unexpectedly, decreasing the [Ca(2+)](o) in the medium had a diametrically opposite effect. Under low [Ca(2+)](o) (0.0022 mM) conditions, normal cells were slow and inefficient in their responses, whereas AT cells showed a substantial improvement in all three end points. These findings demonstrate that loss of ATM kinase function deregulates the extracellular calcium-sensing receptor (CaR). This malfunction presumably arises from a post-transcriptional event, since CaR mRNA proved to be normal in AT cells. Together, our data suggest that ATM may mediate cell response to mitogenic factors by tightly regulating the set point of the CaR and thereby modulating the crosstalk between this metabotropic receptor and growth factor receptors. Alternatively, the faulty sensing of extracellular calcium in AT cells may be secondary to a state of chronic oxidative stress attributable to ATM deficiency.
journal_name
Oncogenejournal_title
Oncogeneauthors
Famulski KS,Al-Hijailan RS,Dobler K,Pienkowska M,Al-Mohanna F,Paterson MCdoi
10.1038/sj.onc.1206167subject
Has Abstractpub_date
2003-01-23 00:00:00pages
471-5issue
3eissn
0950-9232issn
1476-5594pii
1206167journal_volume
22pub_type
杂志文章相关文献
ONCOGENE文献大全abstract::Drug-resistant clones selected from FR3T3 rat cells after transfer of neo-BPV1 (Bovine Papillomavirus Type 1) DNA constructs became phenotypically transformed (focal transformation, growth in suspension and tumor formation) soon after selection (approximately 5 generations in culture). A frameshift mutation in ORF E5 ...
journal_title:Oncogene
pub_type: 杂志文章
doi:
更新日期:1990-11-01 00:00:00
abstract::GATA3 is an essential transcription factor that was first identified as a regulator of immune cell function. In recent microarray analyses of human breast tumors, both normal breast luminal epithelium and estrogen receptor (ESR1)-positive tumors showed high expression of GATA3. We sequenced genomic DNA from 111 breast...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1207966
更新日期:2004-10-07 00:00:00
abstract::The Ets family of transcription factors is one of a growing number of master regulators of development. This family was originally defined by the presence of a conserved DNA binding domain, the Ets domain. To date, nearly 30 members of this family have been identified and implicated in a wide range of physiological an...
journal_title:Oncogene
pub_type: 杂志文章,评审
doi:10.1038/sj.onc.1204038
更新日期:2000-12-18 00:00:00
abstract::Secreted frizzled related protein 1 (SFRP 1) is an antagonist of the transmembrane frizzled receptor, a component of the Wnt signaling pathway, and has been suggested to be a candidate tumor suppressor in several human malignancies. Since SFRP 1 is located at chromosome 8 p 11, where lung cancers also exhibit frequent...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1208777
更新日期:2005-09-15 00:00:00
abstract::The human c-rel gene (REL), encoding an NF-kappaB transcription factor, is amplified or mutated in several human B-cell lymphomas and can transform chicken lymphoid cells in vitro. We have previously shown that certain deletions of C-terminal transactivation sequences enhance REL's transforming ability in chicken sple...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1208902
更新日期:2005-11-10 00:00:00
abstract::A selective switch from expression of Shc1 gene to Shc3 occurs with maturation of neuronal precursors into postmitotic neurons. Previous studies showed that in the embryo, Shc1 is maximally expressed in dividing CNS stem cells while it is silenced in mature neurons, where it is replaced by Shc3. Under normal condition...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1208708
更新日期:2005-08-04 00:00:00
abstract::Cancer cells enhance their glycolysis, producing lactate, even in the presence of oxygen. Glycolysis is a series of ten metabolic reactions catalysed by enzymes whose expression is most often increased in tumour cells. HKII and phosphoglucose isomerase (PGI) have mainly an antiapoptotic effect; PGI and glyceraldehyde-...
journal_title:Oncogene
pub_type: 杂志文章,评审
doi:10.1038/onc.2014.320
更新日期:2015-07-01 00:00:00
abstract::EDD (E3 isolated by differential display), located at chromosome 8q22.3, is the human orthologue of the Drosophila melanogaster tumour suppressor gene 'hyperplastic discs' and encodes a HECT domain E3 ubiquitin protein-ligase. To investigate the possible involvement of EDD in human cancer, several cancers from diverse...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1206775
更新日期:2003-08-07 00:00:00
abstract::Accumulating evidences have shown the association between aberrantly expressed microRNAs (miRs) and cancer, where these small regulatory RNAs appear to dictate the cell fate by regulating all the main biological processes. We demonstrated the responsibility of the circuitry connecting the oncomiR-221&222 with the tumo...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2015.357
更新日期:2016-06-09 00:00:00
abstract::Ras genes, frequently mutated in human tumors, promote malignant transformation. Ras transformation requires membrane anchorage, which is promoted by Ras farnesylcysteine carboxymethylester and by a second signal. Previously we showed that the farnesylcysteine mimetic, farnesylthiosalicylic acid (FTS) disrupts Ras mem...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1204950
更新日期:2001-11-08 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::Cancer cells show deviant behavior that induces apoptotic signaling. To survive, cancer cells typically acquire changes enabling evasion of death signals. One way they do this is by increasing the expression of anti-apoptotic BCL-2 proteins. Anti-apoptotic BCL-2 family proteins antagonize death signaling by forming he...
journal_title:Oncogene
pub_type: 杂志文章,评审
doi:10.1038/onc.2009.52
更新日期:2008-12-01 00:00:00
abstract::Retinoids have been shown to inhibit the growth of a number of human tumor cells, including several ovarian adenocarcinoma cell lines. All-trans retinoic acid (RA) is an effective growth suppressor of CA-OV3 cells but not SK-OV3 cells. Since the effects of RA are known to be mediated via the nuclear receptors (RARs an...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1202208
更新日期:1998-12-03 00:00:00
abstract::P16 was originally discovered by its ability to interact with CDK4 and to specifically inhibit the catalytic activity of the CDK4/D1 kinase. Increased attention has focused on the p16 gene because of its location on chromosome 9p21, a region involved in chromosomal rearrangements in a large number of tumor types. The ...
journal_title:Oncogene
pub_type: 杂志文章
doi:
更新日期:1995-11-16 00:00:00
abstract::The quail Pax-6 gene is expressed from two promoters named P0 and P1. P0 promoter is under the control of a neuroretina-specific enhancer (EP). This enhancer activates the P0 promoter specifically in neuroretina cells and in a developmental stage-dependent manner. The EP enhancer binds efficiently, as revealed by sout...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1202406
更新日期:1999-01-28 00:00:00
abstract::Platelet-derived growth factor (PDGF) and vascular endothelial growth factor define a family of dimeric proteins characterized by eight conserved cysteine residues involved in disulfide bonds. Thirteen non-cysteine residues conserved among the platelet-derived/vascular endothelial growth factors were individually muta...
journal_title:Oncogene
pub_type: 杂志文章
doi:
更新日期:1993-03-01 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::KLF6, a ubiquitously expressed Krüppel-like transcription factor, is frequently inactivated in human cancer and has significant roles in cellular proliferation, apoptosis, differentiation and development. A key mechanism of KLF6-mediated growth suppression is through p53-independent transactivation of p21. Several can...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2012.457
更新日期:2013-09-19 00:00:00
abstract::Overexpression of hepatocyte growth factor (HGF), also called scatter factor (SF), and its receptor c-Met are associated with poor prognosis for cancer patients. In particular, breast cancer cells can produce HGF that acts in a paracrine as well as in an autocrine manner. Therefore, HGF and c-Met are putative targets ...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1207063
更新日期:2003-11-20 00:00:00
abstract::Polyomavirus large T-antigen (PyLT-Ag), a nucleophosphoprotein essential for regulating viral gene expression, modulates the cell cycle by binding to the Rb tumor suppressor gene product. PyLT-Ag/Rb binding is essential for in vitro immortalization. However, the effect of PyLT-Ag on apoptosis has not been extensively ...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1204015
更新日期:2000-12-14 00:00:00
abstract::The W locus of mice encodes the c-kit receptor tyrosine kinase. Recently, we characterized a novel mutant allele, Wn, and demonstrated that the c-kit protein synthesized in Wn/Wn cultured mast cells (CMC) was reduced in size and not expressed on their surface (Tsujimura et al., 1993). In this study, we further examine...
journal_title:Oncogene
pub_type: 杂志文章
doi:
更新日期:1994-01-01 00:00:00
abstract::Cbl proteins are ubiquitin protein ligases, which ubiquitinate activated tyrosine kinases and target them for degradation. Both c-Cbl and Cbl-b have an ubiquitin associated (UBA) domain at their C-terminal end. We observed that high molecular weight ubiquitinated proteins constitutively coimmunoprecipitated with trans...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1207952
更新日期:2004-09-16 00:00:00
abstract::Matrix metalloprotease-1 (MMP1) is an important mediator of tumorigenesis, inflammation and tissue remodeling through its ability to degrade critical matrix components. Recent studies indicate that stromal-derived MMP1 may exert direct oncogenic activity by signaling through protease-activated receptor-1 (PAR1) in car...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2013.157
更新日期:2014-04-24 00:00:00
abstract::A hallmark of cancer is the deregulation of cell-cycle machinery, ultimately facilitating aberrant proliferation that fuels tumorigenesis and disease progression. Particularly, in breast cancers, cyclin D1 has a crucial role in the development of disease. Recently, a highly specific inhibitor of CDK4/6 activity (PD-03...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2010.154
更新日期:2010-07-15 00:00:00
abstract::The human T-cell leukemia virus type 1 (HTLV-1) was the first retrovirus discovered to be causative of a human cancer, adult T-cell leukemia. The transforming entity of HTLV-1 has been attributed to the virally-encoded oncoprotein, Tax. Unlike the v-onc proteins encoded by other oncogenic animal retroviruses that tran...
journal_title:Oncogene
pub_type: 杂志文章,评审
doi:10.1038/onc.2010.537
更新日期:2011-03-24 00:00:00
abstract::Ferritin is the major intracellular iron storage protein that sequesters excess free iron to minimize generation of iron-catalysed reactive oxygen species. We previously demonstrated that expression of ferritin heavy chain (ferritin H) was induced by pro-oxidants, which is a part of cellular antioxidant response to pr...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1208901
更新日期:2005-11-17 00:00:00
abstract::tal-1 deletions are caused by a site specific recombination, which exclusively occurs in 12-26% of T-cell acute lymphoblastic leukemias (T-ALL). In a previous study on a large series of T-ALL we demonstrated an apparent preferential occurrence of tal-1 deletions in CD3- and CD3+ alpha beta lineage T-ALL with TcR-delta...
journal_title:Oncogene
pub_type: 杂志文章
doi:
更新日期:1994-07-01 00:00:00
abstract::We studied loss of heterozygosity (LOH) in chromosome 7q in order to determine the location of a putative tumor suppressor gene (TSG) in human epithelial ovarian carcinomas. Samples were obtained from 26 primary ovarian carcinomas at the time of staging laparotomy. Paired normal and tumoral DNAs were used as templates...
journal_title:Oncogene
pub_type: 杂志文章
doi:
更新日期:1995-07-20 00:00:00
abstract::In a previous work we provided preliminary evidence of the existence of a putative tumor suppressor gene region on the distal part of chromosome 4 in gamma-radiation-induced T-cell lymphomas of (C57BL/6J x RF/J) F1 hybrid mice. This region, named as TLSR2 (Thymic Lymphoma Suppressor Region 2), was located centered at ...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1202009
更新日期:1998-08-20 00:00:00
abstract::Targeting Bruton tyrosine kinase (BTK) by ibrutinib is an effective treatment for patients with relapsed/refractory mantle cell lymphoma (MCL). However, both primary and acquired resistance to ibrutinib have developed in a significant number of these patients. A combinatory strategy targeting multiple oncogenic pathwa...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2016.155
更新日期:2016-12-01 00:00:00