Molecular Cloning, Expression, and Characterization of Angiopoietin-related Protein

Kim, Injune; Moon, Sang Ok; Koh, Keum Nim; Kim, Hyun; Uhm, Chang Sub; Kwak, Hee Jin; Kim, Nam Gyun; Koh, Gou Young

doi:10.1074/jbc.274.37.26523

Cited by 181 publications

(181 citation statements)

References 24 publications

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“…ARP2 acts as an anti-apoptotic factor on vascular endothelial cells (Kim et al, 1999). CP is responsible for the accumulation of copper ions at the apical growth cone of newly forming blood vessels (Raju et al, 1982).…”

Section: Discussionmentioning

confidence: 99%

Identification of human renal cell carcinoma associated genes by suppression subtractive hybridization

et al. 2001

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Renal cell carcinoma (RCC) accounts for approximately 3% of adult malignancies and 1.4% of cancer-related deaths (Reis and Faria, 1994). The prognosis of RCC remains poor. One third of the patients already have metastases when first consulting the hospital. Another 30-40% of patients develop metastases after surgical excision of the primary tumour (Ravaud and Debled, 1999). RCC are radioresistant (Nieder et al, 1996) and more than 80% are chemoresistant (Mickisch, 1994). Since RCC are presumed to be immunogenic, several clinical trials are exploring the efficacy of cytokines, mainly interleukin 2 (IL2) and/or interferon-α (IFNα), and the transfer of lymphokine-activated killer cells (Hofmockel et al, 1997;Bukowski, 2000;Hoffman et al, 2000). Despite these new options, the median survival time of patients with metastatic disease still remains only 6-8 months and the overall 5-year survival rate is less than 5% (Moch et al, 2000;Motzer and Russo, 2000). Thus, there is an urgent requirement for alternative therapeutic modalities.The current strategy is to design therapeutic approaches based on specific biological features of each tumour type. These include (i) the aberrant expression of genes which can be recognized by the immune system as foreign (Pawelec et al, 1999;Wang and Rosenberg, 1999;Bremers and Parmiani, 2000); (ii) gene products related to the formation of new blood vessels (neoangiogenesis), since they are essential for tumour expansion and metastatic settlement (Harris and Thorgeirsson, 1998;Kerbel, 2000;Rosen, 2000) and (iii) the altered expression of adhesion molecules, matrix-degrading enzymes, their receptors and inhibitors, which are a further requisite of metastatic spread (Huang et al, 1997;Yu et al, 1997).Several technique enable the identification of tumour markers. Subtractive hybridization (Lamar and Palmer, 1984; Kunkel et al, 1985;Kuang et al, 1998), differential display reverse transcription-polymerase chain reaction (DD RT-PCR; Liang and Pardee, 1992) and hybridization of cDNA microarrays (reviewed in Khan et al, 1999) are frequently used to compare the expression patterns between tumour and normal tissue. Other approaches, such as serological screening (SEREX;Sahin et al, 1995) and screening of cytotoxic T lymphocyte activity against an autologous tumour cell line (De Plaen et al, 1988), are especially focused on the identification of immunogenic tumour molecules.We have described recently the successful use of SSH using matched RCC and normal kidney tissue . In this study, we randomly selected 16 genes, which by SSH appeared to be differentially expressed. Differential expression of 9 of these 16 genes could be verified by Northern blot analysis. 2 of the 9 genes appeared to be novel. From the remaining 7 genes, expression of 5 had been associated with the malignant phenotype. To substantiate that SSH is a suitable method for the identification of differentially expressed genes, we performed a SSH with an additional pair of normal renal and RCC tissue and compared the validity of SSH ...

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Section: Discussionmentioning

confidence: 99%

Identification of human renal cell carcinoma associated genes by suppression subtractive hybridization

et al. 2001

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“…Ectopic expression of Ang2 in Ang2 nonexpressing cells promotes tumor angiogenesis when those cells are implanted in nude mice (Tanaka et al, 1999). In vitro experiments have shown that Ang1 has speci®c e ects on endothelial cells: it potently induces chemotactic response (Witzenbichler et al, 1998), network formation , sprouting (Koblizek et al, 1998;Kim et al, 1999) and survival in apoptosis Kim et al, 2000a). Although a recent report indicates that Ang2 (250 ng/ml) stimulates proliferation, migration, and release of nitric oxide in trophoblast cells that are expressing the Tie2 receptor (Dunk et al, 2000), the role of Ang2 on cultured endothelial cells is not known.…”

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confidence: 99%

Angiopoietin-2 at high concentration can enhance endothelial cell survival through the phosphatidylinositol 3′-kinase/Akt signal transduction pathway

Kim¹,

Kim²,

Moon³

et al. 2000

Oncogene

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288

199

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“…1 Tie2 signaling has been shown to be required for later stages of embryonic blood vessel development, [2][3][4] including vascular remodeling, vessel integrity, and maturation. 1,5 In vitro experiments have shown that Ang1 induces endothelial cell (EC) sprouting in vitro, 6,7 and stimulates EC migration 8 and the formation and stabilization of capillary-like networks in culture systems. 9 -11 One of the signaling cascades initiated by Tie2 phosphorylation is the recruitment of Dok-R, 12 a novel docking molecule that on phosphorylation binds to proteins containing Src homology 2 (SH2) domains.…”

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confidence: 99%

Angiogenic Actions of Angiopoietin-1 Require Endothelium-Derived Nitric Oxide

Babaei

Teichert-Kuliszewska

Zhang

et al. 2003

The American Journal of Pathology

163

140

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Angiopoietin1 (Ang1) is a novel angiogenic factor with important actions on endothelial cell (EC) differentiation and vascular maturation. Ang1 has been shown to prevent EC apoptosis through activation of PI3-kinase/ Akt, a pathway that is also known to activate endothelium nitric oxide synthase (eNOS). Therefore, we hypothesized that the angiogenic effects of Ang1 would also be dependent on the PI3-kinase/Akt pathway, possibly mediated by increased eNOS activity and NO release. Treatment of human umbilical vein endothelial cells with recombinant Ang1* (300 ng/ml) for 15 minutes resulted in PI3-kinase-dependent Akt phosphorylation, comparable to that observed with vascular endothelial growth factor (VEGF) (50 ng/ml), and increased NO production in a PI3-kinase/Akt-dependent manner. Capillary-like tube formation induced by Ang1* in fibrin matrix at 24 hours (differentiation index, DI: 13.74 ؎ 0.76 versus control 1.71 ؎ 0.31) was abolished in the presence of the selective PI3-kinase inhibitor, LY294002 (50 mol/L) (DI: 0.31 ؎ 0.31, P < 0.01) or the NOS inhibitor, L-NAME (3 mmol/L) (DI: 4.10 ؎ 0.59, P < 0.01). In subcutaneous Matrigel implants in vivo, addition of recombinant Ang1* or wild-type Ang1 from conditioned media of COS-1 cells transfected with a pFLAG Ang1 expression vector, induced significant neovascularization to a degree similar to VEGF. Finally, angiogenesis in vivo in response to both Ang1 and VEGF was significantly reduced in eNOS-deficient compared with wild-type mice. In summary, our results demonstrate for the first time that endothelialderived NO is required for Ang1-induced angiogenesis, and that the PI3-kinase signaling mediates the activation of eNOS and NO release in response to

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Molecular Cloning, Expression, and Characterization of Angiopoietin-related Protein

Cited by 181 publications

References 24 publications

Identification of human renal cell carcinoma associated genes by suppression subtractive hybridization

Identification of human renal cell carcinoma associated genes by suppression subtractive hybridization

Angiopoietin-2 at high concentration can enhance endothelial cell survival through the phosphatidylinositol 3′-kinase/Akt signal transduction pathway

Angiogenic Actions of Angiopoietin-1 Require Endothelium-Derived Nitric Oxide

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