Veriryhmän ISBT 025 Raph osuus MMP järjestelmässä. . CD151 aktivoi MMP kaskadia

http://atlasgeneticsoncology.org/Genes/CD151ID967ch11p15.html

ISBT 025. Raph veriryhmäjärjestelmä. Geeni CD151. Kr. 11p15.5

LÄHDE: http://www.ncbi.nlm.nih.gov/gv/mhc/xslcgi.cgi?cmd=bgmut/systems_info&system=raph

Raph Blood Group System  Symbol RAPH; Gene locus – CD151 Alleles

Johdanto. MER2 antigeeni määrittää Raph veriryhmäjärjestelmän. (2003). Tämä antigeeni sijaitsee CD151 glykoproteiinissa, joka kuuluu tetraspaniini-proteiinien superperheeseen (TM4SP). Tetraspaniini- nimi tulee siitä, että proteiineilla on neljä konservoitua transmembraanista (TM)  jaksoa rakenteessaan. Proteiinia luonnehdittiin ensiksi trombosyyttipinnoista (GP27), mutta nykyisellään sitä on havaittu laajasti eri kudoksista ja myös punasolupinnoista. Se on adheesiomolekyyli. Kts kuva. http://atlasgeneticsoncology.org/Genes/CD151ID967ch11p15.html

 

• Introduction. MER2 antigen defines the Raph blood group system. As shown recently by Crew et al. (Blood, 2003, 102, p4a) the antigen is located on CD151 glycoprotein which is a member of the four-transmembrane (TM4SF, tetraspanins) superfamily of proteins (show four conserved transmembrane domains). The protein was first characterized on platelet surface (GP27) but, has now been shown to have a wide tissue distribution and is also expressed on the surface of erythrocytes. It is an adhesion molecule.

Geenit. Geeni kromosomissa 11p15.5 on järjestäytynyt 8 exoniin ja on kooltaan 4.3 kb. Exonit 2-8 koodaavat proteiinin.

• The genes. The gene on chromosome 11p15.5 is organized in 8 exons and spans 4.3 kb; exons 2-8 encode the protein.

Proteiinien funktio. Tämä  proteiini tekee interaktion integriineihin ja laminiiniin osallistuessaan soluadheesioon, proliferaatioon ja erilaistumiseen. Se saattaa osallistua munuaisglomeruluksen ja glomerulaarisen peruskalvon rakenteeseen ja kehitykseen. Syöpäsoluissa tämä proteiini lisää motiliteettia, invaasiota ja metastasointia.(Osuus eri  syövissä ja liittymä MMP järjestelmään ( Kirjoitan tästä enemmän MMP blogiin myöhemmin suomennosta, joka   on mainittu  linkissä  http://atlasgeneticsoncology.org/Genes/CD151ID967ch11p15.html )

• Function of proteins. Interacts with alpha-beta integrins and laminin participating in cell adhesion, proliferation and differentiation; may be involved in the structure and development of the glomerulus and the glomerular basement membrane in man. In cancer cells enhances cell motility, invasion and metastasis.

Kudosjakauma. Proteiinia ilmenee monissa kudoksissa kuten epiteelissä, endoteelissä, lihaksessa, munuaiskeräsissä ja munuaistiehyeissä, Schwannin soluissa ja dendriittisoluissa,, fibroblasteissa ja muissa solulinjoissa.

• Tissue distribution. Expressed in many tissues including epithelium, endothelium, muscle, renal glomeruli and tubules, Schwann and dendritic cells; fibroblasts and other cell lines.

Tautiliittymä. Eräillä yksilöillä keho ei pysty ilmentämään täyspituista CD151 proteiinia ja heillä on havaittu glomerulonefriittiä ja munuaisentoiminnan häiriötä.

• Disease association. Failure to express full lenght CD151 was shown to be associated in some individuals with glomeluralonephritis and renal failure (Crew et al., Blood, 2004 104 2217-2223).

Alleeleista. Raph veriryhmä määräytyy yhdestä antigeenista MER2 . Sen kantajaproteiini CD 151 tunnisettiin vuonna 2003 ja sitä on useimmilla ihmisillä. Jos tämä on mutatoitunut proteiini,  yksilöt ovat MER2 negatiivisia. Heillä voi esiintyä munuaisen toiminnan vajautta  ja progressiisivtä kuuroutta, koska   myös simpukassa on samantapaisia  erikoisia "verisuoniglomeruluksia" kuin munuaisissa joiden glomerulusen peruskalvossa CD151 on tärkeä.)

• About the alleles The Raph blood group system is defined by a single antigen MER2, first recognized by a monoclonal antibody MER2. The antigen is expressed on erythrocytes of about 92% of Caucasians but the level of expression of MER2 varies among individuals; the remaining 8% of individuals are MER2 negative.

   Crew et al. (Blood, 2003, 102, p4a) identified CD151 as the protein that carries the MER2 antigen. Sequencing of CD151 gene in four MER2 negative individuals who produced alloanti-MER2, identified specific mutations, one of which, resulting in a frameshift and truncation of the protein, occurred in three patients with renal failure. In the list of alleles the sequence acc. no. BT007397 is taken as reference.

 

Rintasyöpä,, onkogeeni MDM2 ( Mouse Double Minute 2), MMP9

http://www.ncbi.nlm.nih.gov/pubmed/24236052

PLoS One. 2013 Nov 13;8(11):e78794. doi: 10.1371/journal.pone.0078794. eCollection 2013.

MDM2 promotes invasion and metastasis in invasive ductal breast carcinoma by inducing matrix metalloproteinase-9.

Chen X¹, Qiu J, Yang D, Lu J, Yan C, Zha X, Yin Y.

Abstract

The molecular mechanisms that underpin invasive ductal breast cancer (IDC) invasion and metastasis are incompletely understood. The oncogene, mouse double minute 2 (MDM2), has been implicated in the pathogenesis of numerous cancers, where it stimulates the expression of matrix metalloproteinase 9 (MMP9), an important enzyme in the breakdown of the extracellular matrix. However, its role in breast cancer remains poorly understood. This study assessed the clinical significance of MDM2 expression in IDC and used in vitro expression assays to determine the molecular roles of MDM2. Immunohistochemical staining for MMP9 and MDM2 was performed using archived tumor blocks from 321 women who underwent surgical resection for IDC at the First Affiliated Hospital of Nanjing Medical University, China between January 2002 and December 2003. MCF-7 and MDA-MD-231 cell lines were transfected with siRNA targeted against MDM2, or MDM2 was overexpressed using transiently expressed vectors.

The invasion, cell migration and proteolytic capabilities of cells that over- or underexpressed MDM2 was then assessed and compared against control cells, in addition to the consequent effects on MMP9 expression using RT-PCR. In vivo, 54.9% and 49.6% of samples were positive for MMP9 and MDM2 expression, respectively, and their expression was significantly correlated (r² = 0.171, P = 0.012). Moreover, MDM2 expression was markedly correlated with disease-free survival (HR 2.56, 95% CI 1.02-6.40, P = 0.038). In vitro, MDM2 overexpression significantly enhanced cell invasion, migration and proteolysis compared with control cells, and the converse effects were observed after MDM2-siRNA treatment. MDM2 overexpression induced MMP9 expression in a dose-dependent manner. Taken together, these results suggest that high levels of MDM2 are associated with a poorer prognosis in IDC. This might result from increased tumor invasiveness due to enhanced MMP9 expression causing increased extracellular matrix breakdown.

PMID:

24236052

[PubMed - indexed for MEDLINE]

PMCID:

PMC3827260

Free PMC Article

Rintasyöpä, PRMT7, MMP9 , metastaasi

Showing results for protein arginine methyltransferase mmp9. Your search for Protein arginin metyltransferase MMP9 retrieved no results.

Oncotarget. 2014 Dec 26. [Epub ahead of print]

Protein arginine methyltransferase 7 promotes breast cancer cell invasion through the induction of MMP9 expression.

Baldwin RM¹, Haghandish N¹, Daneshmand M², Amin S³, Paris G¹, Falls TJ⁴, Bell JC⁵, Islam S³, Côté J¹.

Author information

Abstract

Recent evidence points to the protein arginine methyltransferase (PRMT) family of enzymes playing critical roles in cancer. PRMT7 has been identified in several gene expression studies to be associated with increased metastasis and decreased survival in breast cancer patients. However, this has not been extensively studied. Here we report that PRMT7 expression is significantly upregulated in both primary breast tumour tissues and in breast cancer lymph node metastases. We have demonstrated that reducing PRMT7 levels in invasive breast cancer cells using RNA interference significantly decreased cell invasion in vitro and metastasis in vivo. Conversely, overexpression of PRMT7 in non-aggressive MCF7 cells enhanced their invasiveness. Furthermore, we show that PRMT7 induces the expression of matrix metalloproteinase 9 (MMP9), a well-known mediator of breast cancer metastasis. Importantly, we significantly rescued invasion of aggressive breast cancer cells depleted of PRMT7 by the exogenous expression of MMP9. Our results demonstrate that upregulation of PRMT7 in breast cancer may have a significant role in promoting cell invasion through the regulation of MMP9. This identifies PRMT7 as a novel and potentially significant biomarker and therapeutic target for breast cancer.

PMID:

25605249

[PubMed - as supplied by publisher]

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