Abstract
To investigate the inhibitory effect of RNA interference (RNAi) on MMP-24 expression and invasiveness of ovarian cancer SKOV(3) cells.
Two pairs of small interfering RNA (siRNA) specific to MMP-24 mRNA were designed and transfected into SKOV(3) cells. RT-PCR and Weste...
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PMID: 19403421
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Abstract
The basement membrane (BM), a specialized network of extracellular matrix macromolecules, surrounds epithelial, endothelial, muscle, fat and nerve cells. During development, immune surveillance and disease states ranging from cancer to fibrosis, host cells penetrate the BM by engaging tissue-invasiv...
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PMID: 18848450
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Abstract
We have recently shown that MBD3 is also involved in maintaining the demethylated and active state of rRNA genes, and that depletion of MBD3 results in hypermethylation of rRNA promoters. The possibility that MBD3 could also trigger DNA demethylation of RNA polymerase II-transcribed genes has not be...
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PMID: 18602768
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Abstract
We summarize the structural, biochemical, and biological properties of GPI-MT-MMPs and present an overview of their expression and role in cancer. We further discuss the potential implications of GPI-anchoring for enzyme function. Finally, we comment on the new scientific challenges that lie ahead t...
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PMID: 18286233
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Abstract
The human matrix metalloproteinase (MMP) gene family includes 24 genes whose regulated expression, together with that of four tissue inhibitors of metalloproteinases (TIMPs), is essential in tissue remodelling and cell signalling. Quantitative real-time-PCR (qPCR) analysis was used to evaluate the s...
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PMID: 18029162
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Abstract
These results suggest more than one human MT5-MMP transcript may exist in the central nervous system....
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PMID: 18062926
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Abstract
Both the gene chip expression analyses as well as PCR indicated expression of MT5-MMP in normal human endometrium and strongly elevated transcript levels in most peritoneal endometriosis lesions analyzed. Moreover we detected enhanced MT5-MMP expression in the eutopic endometrium from patients suffe...
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PMID: 17952761
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Abstract
We found a marked increase in MT6-MMP expression within in situ dysplasia and invasive cancer in 61 samples of human colon cancer. Expression of MT6-MMP in HCT-116 human colon cancer cells promoted tumori-genesis in nude mice. Histologically, the MT6-MMP-expressing tumors demonstrated an infiltrativ...
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PMID: 17513868
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Abstract
P4HI leads to an improvement of AoB-associated LV dysfunction and reduces imbalance of extracellular matrix turnover and hypertrophy-associated gene expression. P4H inhibition could therefore be of value in treatment of myocardial remodelling accompanying pressure overload hypertrophy....
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PMID: 17145199
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Abstract
We can assign unique triple-helical peptidase behaviors to the collagenolytic MMPs. Such differences may be significant for understanding MMP mechanisms of action and aid in the development of selective MMP inhibitors....
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PMID: 17338550
PDF is available here.
Abstract
Murine RECK mRNA expression was accurately quantified using real-time PCR. Among the tumor cells used in the study, osteosarcoma cells showed significantly higher RECK mRNA expression than the others. The RECK expression in the osteosarcoma cells was down-regulated by contact with matrigel-coated cu...
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PMID: 17431385
PDF is available here.
Abstract
We have demonstrated that a single cell approach is a viable methodology for studying the responses of cells to mechanical forces. Furthermore, examining the effects of mechanical loading on a cell-by-cell basis allows us to capture behaviors and details that would otherwise elude studies performed...
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PMID: 17045815
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Abstract
We find that endothelial-cell-derived wnts, acting through Frizzled receptors, induce matrix metalloproteinase (MMP) 2 and MMP9 expression in effector T cells. Blocking wnt signaling, or MMP activity, reduces T cell migration through the basement membrane in vitro and into inflamed skin in vivo. Wnt...
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PMID: 17306568
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Abstract
Receptor activator of NF-kappab ligand (RANKL), a key regulator of osteoclastogenesis, is proteolytically processed and converted to a soluble form. RANKL sheddase and the biologic and pathologic role of RANKL shedding have been undetermined, but the identity of sheddase and its effect on osteoclast...
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PMID: 17966383
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Abstract
We previously reported that OPG deficiency elevated the circulating level of RANKL in mice. Using OPG(-/-) mice, we investigated whether OPG is involved in the shedding of RANKL by cells expressing RANKL. Osteoblasts and activated T cells in culture released a large amount of RANKL in the absence of...
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PMID: 17182555
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Abstract
Matrix metalloproteinases (MMPs) constitute a family of more than 20 endopeptidases. Identification of specific matrix and non-matrix components as MMP substrates showed that, aside from their initial role as extracellular matrix modifiers, MMPs play significant roles in highly complex processes suc...
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PMID: 17562450
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Abstract
In fibroadenoma, ductal carcinoma in situ and invasive ductal carcinoma of the breast 4 groups, the positive immunostaining rate of nm23, MMP-2 and TIMP-2 have significant difference among 4 groups (p < 0.05). In the breast invasive ductal carcinoma, the expression of nm23 and TIMP-2 decreased or th...
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PMID: 17642161
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Abstract
We have used laser confocal microscopy, transmission electron microscopy, and biochemical assays to show that human fibroblasts initiate degradation of collagen through the collagenase activity of the membrane-bound metalloproteinase MT1-MMP. Degradation of natural and reconstituted collagen substra...
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PMID: 16971509
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Abstract
We show that EMILIN1, produced by decidual stromal and smooth muscle uterine cells, is expressed in the stroma and in some instances as a gradient of increasing concentration in the perivascular region of modified vessels. This distribution pattern is consistent with the haptotactic directional migr...
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PMID: 17074837
PDF is available here.
Abstract
We show that EC tube morphogenesis (lumen formation and invasion) is primarily controlled by the TIMP-2 and -3 target membrane type (MT) 1 MMP. Additional targets of these inhibitors include MT2-MMP and ADAM-15, which also regulate EC invasion. Mutagenesis experiments reveal that TIMP-3 requires its...
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PMID: 17030988
PDF is available here.
Abstract
We hypothesized that reorganization of the actin cytoskeleton would increase endothelial cell production and activation of MMP-2 and that this increase would require a MAPK-dependent signaling pathway in endothelial cells. The pharmacological actin depolymerization agent cytochalasin D increased exp...
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PMID: 16672691
PDF is available here.
Abstract
We coupled high-resolution electron microscopy with an ex vivo model of invasion that phenocopies the major steps observed during the transition of carcinoma in situ to frank malignancy. Herein, a triad of membrane-anchored proteases, termed membrane type-1, type-2, and type-3 metalloproteinases, ar...
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PMID: 16983145
PDF is available here.
Abstract
We have determined that the peptide sequence that spans the first cleavage site is susceptible to furin and PC5/6, whereas the second sequence is susceptible to furin and also to PC5/6, PC7 and PACE4. In the structure of the MT1-MMP proenzyme, the R(89)-R-P-R-C(93) site, however, is inaccessible to...
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PMID: 16636666
PDF is available here.
Abstract
We have expressed recombinant epilysin in A549 lung adenocarcinoma cells and found that this resulted in stable and irreversible epithelial to mesenchymal transition (EMT) accompanied by loss of cell surface E-cadherin, proteolytic processing of latent TGF-beta-complexes and increased levels of acti...
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PMID: 16940349
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Abstract
We observed that myogenic differentiation proceeded through three distinct stages of proliferation, elongation and fusion, which are distinguishable by their cellular morphologies and gene expression patterns of proliferation- and differentiation-specific markers. Treatment of the differentiating my...
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PMID: 16926191
PDF is available here.
Abstract
We hypothesize that these two isoflavones can induce a lowering of tumor invasion by decreasing the activity of matrix degrading enzymes. In this study we investigated the effects of genistein and biochanin A on invasive activity of U87MG cells using the Calbiochem in vitro invasion assay system. Ou...
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PMID: 16598420
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Abstract
We compared ovarian expression and localization of Fas, Fas ligand (FasL), casapse-8 and membrane-type1 matrix metalloproteinase (MT1-MMP) in rats treated with dehydroepiandrosterone (DHEA) as a model of PCOS, and in control rats. We found that the numbers of TdT-mediated dUTP-biotin nick end-labeli...
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PMID: 16820958
PDF is available here.
Abstract
To clarify the reason why central fibrosis (CF) is an important histological prognostic factor in small adenocarcinoma (SA) of the lung, tumor tissues from 50 patients with SA < or = 2 cm in diameter were investigated using immunohistochemical and in situ hybridization analysis for factors relating...
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PMID: 16930329
PDF is available here.
Abstract
We show that the collagen substrate causes decreased growth rates and morphological alterations correlated with the invasive phenotype. Electronic transmission microscopy of T98G cells revealed membrane invaginations resembling podosomes, which are typically found in cells in the process of crossing...
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PMID: 16791855
PDF is available here.
Abstract
We discuss the identification of distinct matrix metalloproteinases (MMPs) and their inhibitors that differentially control the processes of capillary tube formation (morphogenesis) versus capillary tube regression in three-dimensional (3D) collagen matrices. This work directly relates to both granu...
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PMID: 17069010
PDF is available here.
Abstract
We have examined the activity of two MT1-MT4-MMP chimaeras in which the hemopexin domain of MT1-MMP has been replaced with that of human or mouse MT4-MMP. We show that MT1-MMP bearing the hemopexin domain of MT4-MMP was incapable of activating pro-MMP-2 or degrading gelatin in cell based assays. Fur...
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PMID: 16686598
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Abstract
We show by mutagenesis and kinetic analysis that it is possible to transfer the MT1-MMP binding affinity of the TIMP-2 AB loop to TIMP-4 but that its transplantation into TIMP-4 does not endow the inhibitor with pro-MMP-2 activating activity. However, transfer of both the AB loop and C-terminal doma...
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PMID: 16777853
PDF is available here.
Abstract
We demonstrate that a subset of integrins, alpha(v)beta(6) and alpha(v)beta(8), are responsible for almost all of the TGF-beta activation in the EMTU. Both alpha(v)beta(8) and alpha(v)beta(6) contribute to fetal tracheal epithelial activation of TGF-beta, whereas only alpha(v)beta(8) contributes to...
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PMID: 16877343
PDF is available here.
Edwin S L ES Chan,
Maria Carmen MC Montesinos,
Patricia P Fernandez,
Avani A Desai,
David L DL Delano,
Herman H Yee,
Allison B AB Reiss,
Michael H MH Pillinger,
Jiang-Fan JF Chen,
Michael A MA Schwarzschild,
Scott L SL Friedman and
Bruce N BN Cronstein
Abstract
We therefore determined whether adenosine and its receptors contribute to the pathogenesis of hepatic fibrosis. 2. As in other tissues and cell types, adenosine is released in vitro in response to the fibrogenic stimuli ethanol (40 mg dl(-1)) and methotrexate (100 nM). 3. Adenosine A(2A) receptors a...
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PMID: 16783407
PDF is available here.
Abstract
Irregular bleeding in HT users is associated with a distinct pattern of MMP and TIMP production that differs from that seen in normal menstrual bleeding and from that seen in contraceptive-related breakthrough bleeding. This suggests that the endometrial balance between MMP and TIMP contributes to v...
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PMID: 16684831
PDF is available here.
Abstract
I collagen, together with proliferating fibroblastic cells. Despite the recognized importance of tumor-stromal interactions, very little is known about the interactions among pancreatic cells, myofibroblasts, and the interstitial matrix. The current study was undertaken to test the hypothesis that t...
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PMID: 16849548
PDF is available here.
Abstract
We examined expression of WNT and the WNT inhibitor, secreted frizzled-related protein (FRP), in RA and OA synovium by reverse transcription-PCR. WNT10B was most frequently detected in RA synovium, and FRP1, FRP2, and FRP4 in OA synovium. Immunohistochemistry localized WNT10B and FRP1 in synovial li...
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PMID: 16735027
PDF is available here.
Abstract
Immunohistochemical reactivity for MT1-MMP, RECK and EMMPRIN was detected predominantly in odontogenic epithelial cells near the basement membrane in tooth germs and benign and malignant ameloblastic tumors. The level of immunoreactivity for MT1-MMP was slightly higher in benign and malignant amelob...
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PMID: 16762015
PDF is available here.
Abstract
The aim of this study was to validate the use of transcriptional profiling as a means of characterizing the complex interactions of the thousands of genes that are expressed during fracture healing. Standard mid-diaphyseal tibia fractures were generated in C57/B6 murine tibiae and the transcriptiona...
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PMID: 16584876
PDF is available here.
Abstract
There was overexpression of TGF-beta in MFS associated with altered hyaluronan synthesis, increased apoptosis, impaired progenitor cell recruitment, and abnormal directional migration. These factors limit tissue repair and are likely to contribute to aneurysm development....
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PMID: 16820603
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Abstract
A unique MMP and TIMP portfolio was observed in ATAAs from MFS compared with non-MFS patients. In addition, MFS samples showed evidence of increased TGF-beta signaling. These differences suggest disparate mechanisms of extracellular matrix remodeling between these 2 groups of patients....
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PMID: 16820601
PDF is available here.
Abstract
We investigated the expression of membrane type-1 (MT1)-MMP, MMP2, MMP9 and TIMP2 mRNAs and their roles in ductal carcinoma in situ (DCIS) and T1 and T2 invasive ductal carcinoma of the breast. We further compared these two types of carcinomas for differences in microvessel density, and expression o...
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PMID: 16807982
PDF is available here.
Abstract
UVA irradiation, dose-dependently (5-20 J/cm2), was shown to impair the morphogenic differentiation of human microvascular endothelial cells (HMECs) on Matrigel. Parallely, UVA down-regulated the expression of MMP-2 and MT1-MMP, both at the protein and the mRNA levels. On the contrary, the productio...
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PMID: 16696942
PDF is available here.
Abstract
We have determined that incomplete glycosylation stimulates extensive autocatalytic degradation and self-inactivation of MT1-MMP. Self-proteolysis commences during the secretory process of MT1-MMP through the cell compartment to the plasma membrane. The strongly negatively charged sialic acid is the...
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PMID: 16627478
PDF is available here.
Abstract
We evaluated the location, origin and activity of MMP-2 in cervical squamous cell carcinomas in comparison with MT1-MMP (MMP-14), TIMP-2 and extracellular matrix metalloproteinase inducer (EMMPRIN). Positive immunostaining for MMP-2 in malignant cells was detected in 83% of the patients. Two pattern...
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PMID: 16425263
PDF is available here.
Abstract
We have now determined that the expression of murine MT1-MMP in murine melanoma B16F1 cells strongly increased the number of metastatic loci in the lungs of syngeneic C57BL/6 mice. In contrast, MT1-MMP did not affect the number of metastatic loci in complement-deficient C57BL/6-C3-/- mice. Our resul...
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PMID: 16778201
PDF is available here.
Abstract
We prepared an in vitro aging model consisting in sequential passages of human aortic smooth muscle cells (AoSMC) in order to evaluate the cell behavior changes during aging. Because matrix metalloproteinases (MMP) are actively involved in matrix remodeling and disease outcome, in our model we found...
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PMID: 16770011
PDF is available here.
Abstract
acute, intermediate, and healed groups. The most remarkable changes were observed in the intermediate group, in which MMP-2 activity peaked and tissue expression of mRNAs for MMP-2 and MT1-MMP were observed in spindle-shaped cells in the neointima, organizing thrombus, and the adventitia. These expr...
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PMID: 16609908
PDF is available here.
Vincent Chabottaux,
Nor Eddine Sounni,
Caroline J Pennington,
William R English,
Frédéric van den Brûle,
Silvia Blacher,
Christine Gilles,
Carine Munaut,
Erik Maquoi,
Carlos Lopez-Otin,
Gillian Murphy,
Dylan R Edwards,
Jean-Michel Foidart and
Agnès Noël
Abstract
We have investigated the involvement of MT4-MMP, a glycosylphosphatidylinositol-anchored protease, in breast cancer progression. Interestingly, immunohistochemical analysis shows that MT4-MMP production at protein level is strongly increased in epithelial cancer cells of human breast carcinomas comp...
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PMID: 16707440
PDF is available here.
Abstract
We investigated whether claudin-1, a component of tight junctions, regulated invasion activity in oral squamous cell carcinoma (OSC) cells. The expression of claudin-1, activity of matrix metalloproteinase (MMP)-2, and cleavage of laminin-5 gamma2 chains were assessed by Western blot analysis, immun...
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PMID: 16707450
PDF is available here.
Abstract
One goal of biomedical research is to reliably construct surrogate tissues for replacement therapy and to promote tissue regeneration. In this issue of Cell, Chun et al. (2006) provide insight into the molecular basis of tissue-specific differentiation. The authors show that remodeling of the extrac...
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PMID: 16678088
PDF is available here.
Abstract
We demonstrate that the membrane-anchored metalloproteinase, MT1-MMP, coordinates adipocyte differentiation in vivo. In the absence of the protease, WAT development is aborted, leaving tissues populated by mini-adipocytes which render null mice lipodystrophic. While MT1-MMP preadipocytes display a c...
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PMID: 16678100
PDF is available here.
Abstract
Diabetic glomerulopathy has been linked to shifts in balance between the synthetic and degradative pathways of the glomerular basement membrane (GBM), a key player in the permselectivity properties of the glomerular wall. The goal of this study was to trace the expression and localization of membran...
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PMID: 16541018
PDF is available here.
Abstract
We examined the influence of CAPE on the gene expression of MMPs (MMP-2, MMP-9, MT1-MMP), tissue inhibitor of metalloproteinase-2 (TIMP-2) and in vitro invasiveness of human fibrosarcoma cells. Dose-dependent decreases in MMP and TIMP-2 mRNA levels were observed in CAPE-treated HT1080 human fibrosar...
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PMID: 16214327
PDF is available here.
Abstract
We showed here that transfection of the MT1-MMP gene into HeLa cells promoted fibronectin-induced cell migration, which was accompanied by fibronectin degradation and reduction of stable focal adhesions, which function as anchors for actin-stress fibers. MT1-MMP expression attenuated integrin cluste...
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PMID: 16473349
PDF is available here.
Abstract
We previously reported that aortic endothelial cells can rearrange their cytoskeletons into complex actin-based structures called podosomes when a constitutively active mutant of Cdc42 is expressed. We now report that transforming growth factor beta (TGF-beta) promotes podosome formation in primary...
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PMID: 16611998
PDF is available here.
Abstract
Activation of Wnt signaling through beta-catenin dysregulation occurs in numerous human tumors, including gastric cancer. The specific consequences of Wnt signaling in gastric cancer, however, are not well characterized. This study shows that the introduction of mutant beta-catenin into gastric canc...
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PMID: 16651426
PDF is available here.
Abstract
We compared the expression and activation of these three factors and their regulation by two mesothelioma associated growth factors, platelet-derived growth factor (PDGF)-BB, and transforming growth factor (TGF)-beta1 in six human mesothelioma and one mesothelial cell line. Polymerase chain reaction...
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PMID: 16447244
PDF is available here.
Jingyan Liang,
Enqi Liu,
Ying Yu,
Shuji Kitajima,
Tomonari Koike,
Yingji Jin,
Masatoshi Morimoto,
Kinta Hatakeyama,
Yujiro Asada,
Teruo Watanabe,
Yasuyuki Sasaguri,
Shigeyuki Watanabe and
Jianglin Fan
Abstract
Overexpression of MMP-12 causes accelerated atherosclerosis in Tg rabbits. These results suggest that macrophage-derived MMP-12 participates in the progression of atherosclerosis....
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PMID: 16636188
PDF is available here.