• Title/Summary/Keyword: Urokinase-type plasminogen activator(u-PA)

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Effect of Eupatorium japonicum Extract on the Metastasis, Invasion and Adhesion of MDA-MB-231 Human Breast Cancer Cells (등골나물 추출물이 인간의 유방암세포인 MDA-MB-231 세포의 이동, 침윤 및 부착에 미치는 영향)

  • Woo, Eun-Young;Park, So-Young;Kwon, Soo-Jin;Kwon, Gyoo-Taik;Kim, Jong-Dae;Lim, Soon-Sung;Yoon, Jung-Han
    • Korean Journal of Food Science and Technology
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    • v.43 no.2
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    • pp.213-219
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    • 2011
  • The metastatic effect of Eupatorium japonicum extract (EJE) on MDA-MB-231 human breast cancer cells was investigated. MDA-MB-231 cells were treated with various concentrations of EJE (0, 5, 10 and $20{\mu}g/mL$). EJE inhibited cell migration, invasion and adhesion of MDA-MB-231 cells in dose-dependent manners. Gelatin zymography exhibited that EJE significantly down regulated secretion of matrix metalloproteinase (MMP)-9 and MMP-2. EJE decreased the protein levels of tissue inhibitor of metalloproteinase (TIMP)-1 but increased TIMP-2 levels. Additionally, EJE reduced the protein and mRNA levels of urokinase-type plasminogen activator (uPA), vascular endothelial growth factor (VEGF) and intercellular adhesion molecule (ICAM). In several solvent fractions of EJE, the hexane fraction markedly decreased MDAMB-231 cell migration. Thus, these finding suggest that EJE may be a potential antimetastatic agent, which can considerably inhibit the metastatic and invasive capacity of breast cancer cells.

mRNA Expression Differences of uPA, uPAR in Eutopic Endometrium of Advanced Stage Endometriosis Patients (중증 자궁내막증 환자의 자궁내막과 정상인 자궁내막에서 uPA, uPAR mRNA 발현의 차이에 관한 연구)

  • Hur, Sung Eun;Lee, Ji Young;Lee, Woon Jung;Chung, Hye-Sung;Chung, Hye Won
    • Clinical and Experimental Reproductive Medicine
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    • v.33 no.4
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    • pp.229-236
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    • 2006
  • Objective: We investigated the expression of uPA and uPAR in eutopic endometrium of advanced stage endometriosis and control patients. Methods: The 33 endometriosis patients and 32 controls were enrolled. Endometrial samples were obtained from 65 premenopausal women aged 29-44 years, undergoing laparoscopic surgery or hysterectomy for non-malignant lesions. Sufficient samples were collected from 33 patients with endometriosis stage Ill and IV and 32 controls without endometriosis confirmed by laparoscopic surgery. The mRNA expression of uPA and uPAR from eutopic endometrium were analyzed by RT-QC PCR. Results: The mRNAs of uPA and uPAR were expressed in eutopic endometrium from endometriosis and normal controls throughout the menstrual cycle. Uterine endometrium from women with endometriosis expresses significantly (p<0.05) higher levels of u-PA mRNA than endometrium from normal women without endometriosis in the proliferative phase. There were no significant differences in expression of uPAR in eutopic endometrium between controls and endometriosis patients. Conclusion: These results suggest that eutopic endometrium from endometriosis patients may be more invasive and prone to peritoneal implantation because of greater u-PA mRNA expression than endometrium from women without endometriosis. Thus, increased proteolytic activity may be one etiology for the invasive properties of the endometrium resulting in the development of endometriosis.

Peroxiredoxin 6 Promotes Lung Cancer Cell Invasion by Inducing Urokinase-Type Plasminogen Activator via p38 Kinase, Phosphoinositide 3-Kinase, and Akt

  • Lee, Seung Bum;Ho, Jin-Nyoung;Yoon, Sung Hwan;Kang, Ga Young;Hwang, Sang-Gu;Um, Hong-Duck
    • Molecules and Cells
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    • v.28 no.6
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    • pp.583-588
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    • 2009
  • The peroxiredoxin family of peroxidase has six mammalian members (Prx 1-6). Considering their frequent up-regulation in cancer cells, Prxs may contribute to cancer cells' survival in face of oxidative stress. Here, we show that Prx 6 promotes the invasiveness of lung cancer cells, accompanied by an increase in the activity of phosphoinositide 3-kinase (PI3K), the phosphorylation of p38 kinase and Akt, and the protein levels of uPA. Functional studies reveal that these components support Prx 6-induced invasion in the sequence p38 kinase/PI3K, Akt, and uPA. The findings provide a new understanding of the action of Prx 6 in cancer.

Plasminogen Activator Inhibitor Type 1 Gene Polymorphism in Patients with Minimal Change Nephrotic Syndrome (소아 신증후군 환자에서 Plasminogen Activator Inhibitor Type 1 유전자 다형성)

  • Kim Young-Min;Hong Hyun-Kee;Kim Sung-Do;Cho Byoung-Soo
    • Childhood Kidney Diseases
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    • v.8 no.1
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    • pp.26-32
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    • 2004
  • Purpose : Hypercoagulability is present in patients with nephrotic syndrome. Plasminogen activator inhibitor type 1(PAI-1) is a major inhibitor of plasminogen activators. PAI-1 inactivates both tissue plasminogen activator(tPA) and urokinase plasminogen activator(uPA) by rapid formation of inactive 1:1 stoichiometric complexes. Recently some studies showed that the enhanced PAI-1 expression may be involved in the intraglomerular fibrinogen/fibrinrelated antigen deposition seen in nephrotic syndrome. Methods : PAI-1 gene promoter -844(G/A) polymorphism was evaluated in 146 children with minimal change nephrotic syndrome(MCNS) and 230 control subjects. The patients with MCNS were subdivided into 85 infrequent-relapser(IR) group and 61 frequent relapser(FR) group. PCR of PAI-1 gene promoter region including -844(G/A) and RFLP using the restriction enzyme Xhol were performed for each DNA samples extracted from the groups. Results : The distribution of PAI-1 genotype in the control group was G/G 81(32.5%), A/A 42(16.9%), and G/A 126(50.6%). The distribution of PAI-1 genotypes in the IR group of MCNS was G/G 29(34.1%), A/A 15(17.7%), and G/A 41(48.2%). The distribution of PAI-1 genotype in the FR group of MCNS was G/G 17(27.9%), A/A 18(29.5%), and G/A 26(42.6%). There was a significantly increased frequency of A/A genotype(P=0.0251) in the FR group of MCNS. Conclusion : Our results indicate that the PAI-1 gene promoter A/A genotype may be associated with the FR in MCNS.

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The Candidate Tumor Suppressor Gene SLC8A2 Inhibits Invasion, Angiogenesis and Growth of Glioblastoma

  • Qu, Mingqi;Yu, Ju;Liu, Hongyuan;Ren, Ying;Ma, Chunxiao;Bu, Xingyao;Lan, Qing
    • Molecules and Cells
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    • v.40 no.10
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    • pp.761-772
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    • 2017
  • Glioblastoma is the most frequent and most aggressive brain tumor in adults. Solute carrier family 8 member 2 (SLC8A2) is only expressed in normal brain, but not present in other human normal tissues or in gliomas. Therefore, we hypothesized that SLC8A2 might be a glioma tumor suppressor gene and detected the role of SLC8A2 in glioblastoma and explored the underlying molecular mechanism. The glioblastoma U87MG cells stably transfected with the lentivirus plasmid containg SLC8A2 (U87MG-SLC8A2) and negative control (U87MG-NC) were constructed. In the present study, we found that the tumorigenicity of U87MG in nude mice was totally inhibited by SLC8A2. Overexpression of SLC8A2 had no effect on cell proliferation or cell cycle, but impaired the invasion and migration of U87MG cells, most likely through inactivating the extracellular signal-related kinases (ERK)1/2 signaling pathway, inhibiting the nuclear translocation and DNA binding activity of nuclear factor kappa B ($NF-{\kappa}B$), reducing the level of matrix metalloproteinases (MMPs) and urokinase-type plasminogen activator (uPA)-its receptor (uPAR) system (ERK1/2-$NF-{\kappa}B$-MMPs/uPA-uPAR), and altering the protein levels of epithelial to mesenchymal transitions (EMT)-associated proteins E-cardherin, vimentin and Snail. In addition, SLC8A2 inhibited the angiogenesis of U87MG cells, probably through combined inhibition of endothelium-dependent and endothelium-nondependent angiogenesis (vascular mimicry pattern). Totally, SLC8A2 serves as a tumor suppressor gene and inhibits invasion, angiogenesis and growth of glioblastoma.

Tissue- and Reproductive Organ-specific Expression of Protease Nexin-1 in Sprague-Dawley Rat (흰쥐에서 단백질 분해효소 저해제, Nexin-1의 조직 및 생식기관 특이적 유전자 발현)

  • 고정재;김남근;김진규;최명진;정형민;서승염;김윤희;이현환;차광열
    • Development and Reproduction
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    • v.2 no.2
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    • pp.135-140
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    • 1998
  • Protease Nexin-1 (PN-1) inhibits the activity of several serine proteases including thrombin, urokinase (uPA)-type plasminogen activator and trypsin. Tissue- and reproductive organ-specific mRNA levels of the PN-1 were investigated in Sprague-Dawley adult rat. PN-1 mRNA expression in rats was found in brain (forebrain, hindbrain), heart, liver, lung, ovary and oviduct. The level of PN-1 mRNA in male and female among the tissues was the highest in forebrain of the female. PN-1 expression in reproductive organs was found only in ovary and oviduct. These results suggest that PN-1 expression is dependent on the sex and may be related to folliculogenesis and early embryogenesis.

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Anti-metastasis Activity of Black Rice Anthocyanins Against Breast Cancer: Analyses Using an ErbB2 Positive Breast Cancer Cell Line and Tumoral Xenograft Model

  • Luo, Li-Ping;Han, Bin;Yu, Xiao-Ping;Chen, Xiang-Yan;Zhou, Jie;Chen, Wei;Zhu, Yan-Feng;Peng, Xiao-Li;Zou, Qiang;Li, Sui-Yan
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.15
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    • pp.6219-6225
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    • 2014
  • Background: Increasing evidence from animal, epidemiological and clinical investigations suggest that dietary anthocyanins have potential to prevent chronic diseases, including cancers. It is also noteworthy that human epidermal growth factor receptor 2 (ErbB2) protein overexpression or ErbB2 gene amplification has been included as an indicator for metastasis and higher risk of recurrence for breast cancer. Materials and Methods: The present experiments investigated the anti-metastasis effects of black rice anthocyanins (BRACs) on ErbB2 positive breast cancer cells in vivo and in vitro. Results: Oral administration of BRACs (150 mg/kg/day) reduced transplanted tumor growth, inhibited pulmonary metastasis, and decreased lung tumor nodules in BALB/c nude mice bearing ErbB2 positive breast cancer cell MDA-MB-453 xenografts. The capacity for migration, adhesion, motility and invasion was also inhibited by BRACs in MDA-MB-453 cells in a concentration dependent manner, accompanied by decreased activity of a transfer promoting factor, urokinase-type plasminogen activator (u-PA). Conclusions: Together, our results indicated that BRACs possess anti-metastasis potential against ErbB2 positive human breast cancer cells in vivo and in vitro through inhibition of metastasis promoting molecules.