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Roles of Arrest-Defective Protein 1(225) and Hypoxia-Inducible Factor 1 alpha in Tumor Growth and Metastasis
DC Field | Value | Language |
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dc.contributor.author | Lee, Mi-Ni | - |
dc.contributor.author | Lee, Shi-Nai | - |
dc.contributor.author | Kim, Se-Hee | - |
dc.contributor.author | Kim, Bora | - |
dc.contributor.author | Seo, Ji Hae | - |
dc.contributor.author | Choi, Jae-Hoon | - |
dc.contributor.author | Lee, Mi-Ran | - |
dc.contributor.author | Yoo, Ji-Young | - |
dc.contributor.author | Lee, Seung-Taek | - |
dc.contributor.author | Oh, Goo Taeg | - |
dc.contributor.author | Kim, Kyu-Won | - |
dc.contributor.author | Ryeom, Sandra | - |
dc.contributor.author | Kim, Hwan-Mook | - |
dc.contributor.author | Kim, Jeong Hun | - |
dc.contributor.author | Park, Jong-Gil | - |
dc.contributor.author | Yim, Sun Hee | - |
dc.contributor.author | Park, Ji-Hyeon | - |
dc.contributor.author | Jung, Bo-Kyung | - |
dc.date.accessioned | 2012-06-29T02:04:56Z | - |
dc.date.available | 2012-06-29T02:04:56Z | - |
dc.date.issued | 2010-03-17 | - |
dc.identifier.citation | JOURNAL OF THE NATIONAL CANCER INSTITUTE; Vol.102 6; 426-442 | ko_KR |
dc.identifier.issn | 0027-8874 | - |
dc.identifier.uri | https://hdl.handle.net/10371/77880 | - |
dc.description.abstract | Vascular endothelial growth factor A (VEGFA), a critical mediator of tumor angiogenesis, is a well-characterized target of hypoxia-inducible factor 1 (HIF-1). Murine arrest-defective protein 1A (mARD1A(225)) acetylates HIF-1 alpha, triggering its degradation, and thus may play a role in decreased expression of VEGFA. We generated Apc(Min/+)/mARD1A(225) transgenic mice and quantified growth of intestinal polyps. Human gastric MKN74 and murine melanoma B16F10 cells overexpressing mARD1A(225) were injected into mice, and tumor growth and metastasis were measured. VEGFA expression and microvessel density in tumors were assessed using immunohistochemistry. To evaluate the role of mARD1A(225) acetylation of Lys532 in HIF-1 alpha, we injected B16F10-mARD1A(225) cell lines stably expressing mutant HIF-1 alpha/K532R into mice and measured metastasis. All statistical tests were two-sided, and P values less than .05 were considered statistically significant. Apc(Min/+)/mARD1A(225) transgenic mice (n = 25) had statistically significantly fewer intestinal polyps than Apc(Min/+) mice (n = 21) (number of intestinal polyps per mouse: Apc(Min/+) mice vs Apc(Min/+)/mARD1A(225) transgenic mice, mean = 83.4 vs 38.0 polyps, difference = 45.4 polyps, 95% confidence interval [CI] = 41.8 to 48.6; P < .001). The growth and metastases of transplanted tumors were also statistically significantly reduced in mice injected with mARD1A(225)-overexpressing cells than in mice injected with control cells (P < .01). Moreover, overexpression of mARD1A(225) decreased VEGFA expression and microvessel density in tumor xenografts (P < .04) and Apc(Min/+) intestinal polyps (P = .001). Mutation of lysine 532 of HIF-1 alpha in B16F10-mARD1A(225) cells prevented HIF-1 alpha degradation and inhibited the antimetastatic effect of mARD1A(225) (P < .001). mARD1A(225) may be a novel upstream target that blocks VEGFA expression and tumor-related angiogenesis. | ko_KR |
dc.language.iso | en | ko_KR |
dc.publisher | OXFORD UNIV PRESS INC | ko_KR |
dc.title | Roles of Arrest-Defective Protein 1(225) and Hypoxia-Inducible Factor 1 alpha in Tumor Growth and Metastasis | ko_KR |
dc.type | Article | ko_KR |
dc.contributor.AlternativeAuthor | 이미니 | - |
dc.contributor.AlternativeAuthor | 이시내 | - |
dc.contributor.AlternativeAuthor | 김세희 | - |
dc.contributor.AlternativeAuthor | 김보라 | - |
dc.contributor.AlternativeAuthor | 정보경 | - |
dc.contributor.AlternativeAuthor | 서지해 | - |
dc.contributor.AlternativeAuthor | 박지현 | - |
dc.contributor.AlternativeAuthor | 최재훈 | - |
dc.contributor.AlternativeAuthor | 임선희 | - |
dc.contributor.AlternativeAuthor | 이미란 | - |
dc.contributor.AlternativeAuthor | 박종길 | - |
dc.contributor.AlternativeAuthor | 유지영 | - |
dc.contributor.AlternativeAuthor | 김정훈 | - |
dc.contributor.AlternativeAuthor | 이승택 | - |
dc.contributor.AlternativeAuthor | 김환묵 | - |
dc.contributor.AlternativeAuthor | 염산드라 | - |
dc.contributor.AlternativeAuthor | 김규원 | - |
dc.contributor.AlternativeAuthor | 오구택 | - |
dc.identifier.doi | 10.1093/jnci/djq026 | - |
dc.citation.journaltitle | JOURNAL OF THE NATIONAL CANCER INSTITUTE | - |
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