Abstract:
:Angiogenesis is essential for tumor growth and blocking this process might be a valid tool for the control of cancer growth. We showed previously that tumor angiogenesis in integrin alpha1-null mice is reduced compared to that of wild type animals and that over-expression of matrix metalloproteinase 9 (MMP-9) in the alpha1-null and consequent generation of angiostatin (an inhibitor of endothelial cell growth) from circulating plasminogen was implicated in the mechanism of tumor inhibition. Our findings suggested that secretion of excess MMPs generates inhibitors of endothelial cell proliferation, including but not necessarily limited to angiostatin, resulting ultimately in auto-inhibition of angiogenesis. Thus MMP inhibitors used as anti-tumor drugs might in fact cause a paradoxical increase in tumor angiogenesis and tumor growth. In order to determine whether MMP-9 expression was directly involved in the regulation of tumor growth, we specifically inhibited or enhanced MMP-9 synthesis in vitro and in vivo, and subsequently analysed primary endothelial cell proliferation and angiostatin synthesis, as well as tumor vascularization and development. We provide evidence that reduction of plasma levels of MMP-9 in either normal or integrin alpha1-null mice leads to decreased synthesis of angiostatin and consequent increased tumor growth and vascularization. In contrast, specifically enhancing MMP-9 expression in vivo caused a reduction in tumor vascularization. These findings are the opposite to other studies suggesting a pro-tumorigenic role for MMP-9, and may account for some of the recently observed failures of anti MMP therapy in tumor treatment.
journal_name
Oncogenejournal_title
Oncogeneauthors
Pozzi A,LeVine WF,Gardner HAdoi
10.1038/sj.onc.1205045subject
Has Abstractpub_date
2002-01-10 00:00:00pages
272-81issue
2eissn
0950-9232issn
1476-5594journal_volume
21pub_type
杂志文章相关文献
ONCOGENE文献大全abstract::Over 70% of human breast cancers are estrogen receptor-positive (ER+), most of which express MYB. In these and other cell types, the MYB transcription factor regulates the expression of many genes involved in cell proliferation, differentiation, tumorigenesis, and apoptosis. So far, no clear link has been established ...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/s41388-019-0789-3
更新日期:2019-06-01 00:00:00
abstract::Mutations of the RET proto-oncogene are found in the majority of patients with the inherited cancer syndrome multiple endocrine neoplasia type 2 (MEN 2). A minority of cases, however, have no detectable RET mutation and there is considerable phenotypic variation within and among MEN 2 families with the same RET mutati...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1207826
更新日期:2005-02-03 00:00:00
abstract::Evi5 is a common site of retroviral integration in T-cell lymphomas of AKXD mice. Mapping studies have localized Evi5 to a region approximately 18 kb upstream of another common viral integration site, Gfi1, on mouse chromosome 5 (Liao X, Jenkins NA and Copeland NG, (1995a). J. Virol., 69, 7132-7137). Gfi1 encodes a zi...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1200929
更新日期:1997-03-06 00:00:00
abstract::The DCC (deleted in colorectal cancer) gene was originally identified as a candidate tumour suppressor gene in colon carcinogenesis on the basis of allelic losses in chromosome 18q.21 in 70% of colon cancers. Reverse transcriptase polymerase chain reaction (RT-PCR) of DCC mRNA suggests that DCC expression may also be ...
journal_title:Oncogene
pub_type: 杂志文章
doi:
更新日期:1996-08-15 00:00:00
abstract::Clonogenic murine B cell precursors are normally ultrasensitive to apoptosis following genotoxic exposure in vitro but can be protected by expression of an E mu-BCL-2 transgene. Such exposures are likely to be mutagenic. This in turn suggests that a level of in vivo genotoxic exposure that usually has minimal patholog...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1202721
更新日期:1999-07-01 00:00:00
abstract::Structural rearrangements involving chromosome 13 are frequently seen in B-cell chronic lymphocytic leukaemia. The presence of reciprocal translocations involving 13q14 in 10-15% of cases pinpoints the location of a gene important in leukaemogenesis. In order to characterise the exact location of the 13q14 breakpoint,...
journal_title:Oncogene
pub_type: 杂志文章
doi:
更新日期:1993-06-01 00:00:00
abstract::Cell migration is an integral component of metastatic disease. The ability of cells to transit between mesenchymal and amoeboid modes of migration has complicated the development of successful therapies designed to target cell migration as a means of inhibiting metastasis. Therefore, investigations of the mechanisms t...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2010.516
更新日期:2011-03-10 00:00:00
abstract::Superior cervical ganglia 10 (SCG10), as a microtubule (MT) destabilizer, maintains MT homeostasis and has a critical role in neuronal development, but its function in tumorigenesis has not been characterized. In the present study, we demonstrated that p21-activated kinase 4 (PAK4)-mediated SCG10 phosphorylation regul...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2013.296
更新日期:2014-06-19 00:00:00
abstract::Acetylation is thought to be a key event for p53 activation. We demonstrate that p14ARF-induced senescence of human mammary epithelial cells (MEC) is associated with p53 acetylation and requires hAda3, a component of histone acetyltransferase complexes and a p53 transcriptional coactivator. Expression of the N-termina...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1210462
更新日期:2007-09-20 00:00:00
abstract::The microenvironment of glioblastoma (GBM) contains high levels of inflammatory cytokine interleukin 6 (IL-6), which contributes to promote tumour progression and invasion. The common epidermal growth factor receptor variant III (EGFRvIII) mutation in GBM is associated with significantly higher levels of IL-6. Further...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2014.225
更新日期:2015-05-28 00:00:00
abstract::Bladder cancer is one of the most common causes of death in industrialized countries. New tumor markers and therapeutic approaches are still needed to improve the management of bladder cancer patients. Choline kinase-alpha (ChoKalpha) is a metabolic enzyme that has a role in cell proliferation and transformation. Inhi...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2009.91
更新日期:2009-07-02 00:00:00
abstract::Proliferating cell nuclear antigen (PCNA) has no intrinsic enzymatic function, but functions as a sliding platform to mediate protein interactions with the DNA strand. Many proteins interact with PCNA through a small conserved motif with consensus QxxLxxFF. This work uses Schizosaccharomyces pombe and human cells to a...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1209320
更新日期:2006-05-11 00:00:00
abstract::Mutations in the c-KIT receptor occur somatically in many sporadic Gastrointestinal Stromal Tumors (GIST), and similar mutations have been identified at the germline level in kindreds with multiple GISTs. These mutations activate the tyrosine kinase activity of c-KIT and induce constitutive signaling. To investigate t...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1204704
更新日期:2001-08-16 00:00:00
abstract::Transcription from the rat TGF alpha promoter initiates at two predominant sites (-188 and -58) in a G+C-rich region that does not contain TATA or CAAT motifs. Previous studies using transfected reporter constructs implicated the transcription factor Sp1 in active expression from the promoter, particularly from the -5...
journal_title:Oncogene
pub_type: 杂志文章
doi:
更新日期:1994-11-01 00:00:00
abstract::Previous observations suggest expression of cyclooxygenase-2 to convey macrophage protection towards apoptotic cell death. We reasoned prostaglandin formation and in turn a cAMP increase as the underlying protective principle. Here we report that exposure of macrophages to lipopolysaccharide/interferon-gamma or lipoph...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1201926
更新日期:1998-07-23 00:00:00
abstract::We have previously shown that the death receptor ligand TRAIL (tumor necrosis factor-related apoptosis-inducing ligand) induces an increase of intracellular C(16)-ceramide in sensitive SW480 but not in resistant SW620 cells. Resistance in SW620 cells was overcome by exogenous ceramide, leading us to propose that defec...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2008.468
更新日期:2009-02-26 00:00:00
abstract::The human INK4a gene locus encodes two structurally unrelated tumor suppressor proteins, p16(INK4a) and p14(ARF), which are frequently inactivated in human cancer. Whereas p16(INK4a) acts through engagement of the Rb-cdk4/6-cyclin D pathway, both the pro-apoptotic and cell cycle-regulatory functions of p14(ARF) were s...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1205458
更新日期:2002-05-09 00:00:00
abstract::The rodent S100-related calcium-binding protein, S100A4 induces metastasis in non-metastatic rat and mouse benign mammary cells and co-operates with benign-tumour-inducing changes in two transgenic mouse models, to yield metastatic mammary tumours. Co-transfection of the human gene for S100A4 with pSV2neo into the ben...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1201948
更新日期:1998-07-30 00:00:00
abstract::The tumor suppressor gene phosphatase and tensin homologue (PTEN) regulates the phosphatidylinositol-3'-kinase (PI3K) signaling pathway and has been shown to correlate with poor prognosis in high-grade astrocytomas when mutational inactivation or loss of the PTEN gene occurs. PTEN mutation leads to constitutive activa...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1208427
更新日期:2005-05-19 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::Nuclear factor-kappaB (NF-kappaB) is a dynamic transcription factor that regulates important biological processes involved in cancer initiation and progression. Identifying regulators that control the half-life of NF-kappaB is important to understanding molecular processes that control the duration of transcriptional ...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1211030
更新日期:2008-06-05 00:00:00
abstract::We have previously shown (Smith et al., 1994) that antibodies raised against the growth arrest and DNA damage inducible protein Gadd45 co-precipitate proliferating cell nuclear antigen (PCNA), a protein involved in DNA replication and repair. Here we demonstrate that Gadd45 can directly bind to PCNA using a Far-wester...
journal_title:Oncogene
pub_type: 杂志文章
doi:
更新日期:1995-11-16 00:00:00
abstract::TGF-β is a multifunctional cytokine affecting many cell types and implicated in tissue remodeling processes. Due to its many functions and cell-specific effects, the consequences of TGF-β signaling are process-and stage-dependent, and it is not uncommon that TGF-β exerts distinct and sometimes opposing effects on a di...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2017.140
更新日期:2017-09-07 00:00:00
abstract::It has recently been shown that the high-risk human papillomavirus (HPV) E6 proteins can target the PDZ-domain containing proteins, Dlg, MUPP-1, MAGI-1 and hScrib for proteasome-mediated degradation. However, the E6 proteins from HPV-16 and HPV-18 (the two most common high-risk virus types) differ in their ability to ...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1204719
更新日期:2001-09-06 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::Mouse plasmacytomas induced by pristane oil alone, or in combination with Abelson murine leukemia virus (A-MuLV), regularly carry one of three alternative chromosomal translocations that juxtapose c-myc to immunoglobulin heavy- or light-chain loci. E mu-c-myc transgenic mice develop translocation-free plasmacytomas af...
journal_title:Oncogene
pub_type: 杂志文章
doi:
更新日期:1992-06-01 00:00:00
abstract::Mdm2, a regulator of the p53 tumor suppressor, is frequently overexpressed in lymphomas, including lymphomas that have inactivated p53. However, the biological consequences of Mdm2 overexpression in lymphocytes are not fully resolved. Here, we report that increased expression of Mdm2 in B cells augmented proliferation...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1210788
更新日期:2008-03-06 00:00:00
abstract::To study the interplay of steroid hormones and oncogenes in the control of endometrial cell proliferation and differentiation we have generated cell lines derived from rat endometrium by expressing the immortalizing oncogenes adeno E1A or SV40 large T antigen. These lines are positive for mesenchymal markers and conta...
journal_title:Oncogene
pub_type: 杂志文章
doi:
更新日期:1993-08-01 00:00:00
abstract::Interstitial fluid flow in and around the tumor tissue is a physiologically relevant mechanical signal that regulates intracellular signaling pathways throughout the tumor. Yet, the effects of interstitial flow and associated fluid shear stress on the tumor cell function have been largely overlooked. Using in vitro bi...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2014.397
更新日期:2015-08-27 00:00:00
abstract::An oncogenic mutation (G49A:E17K) in the AKT1 gene has been described recently in human breast, colon, and ovarian cancers. The low frequency of this mutation and perhaps other selective pressures have prevented the isolation of human cancer cell lines that harbor this mutation thereby limiting functional analysis. He...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2009.516
更新日期:2010-04-22 00:00:00