Full metadata record
DC Field | Value | Language |
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dc.contributor.author | 장기석 | - |
dc.date.accessioned | 2018-04-15T07:38:38Z | - |
dc.date.available | 2018-04-15T07:38:38Z | - |
dc.date.issued | 2011-05 | - |
dc.identifier.citation | Oncogene,Vol30,No45[2011],4578p ~ 4667p | en_US |
dc.identifier.issn | 0950-9232 | - |
dc.identifier.uri | https://www.nature.com/articles/onc2011174 | - |
dc.identifier.uri | http://hdl.handle.net/20.500.11754/66646 | - |
dc.description.abstract | Mel-18 has been implicated in several processes in tumor progression, in which the Akt pathway is involved as an important key molecular event. However, the function of Mel-18 in human cancers has not been fully established yet. Here, we examined the effect of Mel-18 on tumor angiogenesis in human breast cancer, and found that Mel-18 was a novel regulator of HIF-1α. Mel-18 negatively regulated the HIF-1α expression and its target gene VEGF transcription during both normoxia and hypoxia. We demonstrated that Mel-18 regulated the HIF-1α expression and activity via the PI3K/Akt pathway. Loss of Mel-18 downregulated Phosphatase and tensin homolog deleted on chromosome 10 (PTEN) expression, consequently activating the PI3K/Akt/MDM2 pathway, and leading to an increase of HIF-1α protein level. Mel-18 modulated the HIF-1α transcriptional activity via regulating the cytoplasmic retention of FOXO3a, a downstream effector of Akt, and recruitment of HIF-1α/CBP complex to the VEGF promoter. Furthermore, our data shows that Mel-18 blocked tumor angiogenesis both in vitro and in vivo. Mel-18 overexpression inhibited in vitro tube formation in human umbilical endothelial cells (HUVECs). Xenografts in NOD/SCID mice derived from stably Mel-18 knocked down MCF7 human breast cancer cells showed increased tumor volume, microvessel density, and phospho-Akt and HIF-1α expression levels. In conclusion, our findings provide that Mel-18 is a novel regulator of tumor angiogenesis through regulating HIF-1α and its target VEGF expressions mediated by the PTEN/PI3K/Akt pathway, suggesting a new tumor-suppressive role of Mel-18 in human breast cancer. | en_US |
dc.language.iso | en | en_US |
dc.publisher | Nature Publishing Group | en_US |
dc.subject | Breast cancer | en_US |
dc.subject | Cell signalling | en_US |
dc.subject | Gene regulation | en_US |
dc.subject | Tumour angiogenesis | en_US |
dc.title | Loss of Mel-18 induces tumor angiogenesis through enhancing the activity and expression of HIF-1 alpha mediated by the PTEN/PI3K/Akt pathway | en_US |
dc.title.alternative | PI3K | en_US |
dc.type | Article | en_US |
dc.relation.no | 45 | - |
dc.relation.volume | 30 | - |
dc.identifier.doi | 10.1038/onc.2011.174 | - |
dc.relation.page | 4578-4589 | - |
dc.relation.journal | ONCOGENE | - |
dc.contributor.googleauthor | Jang, K S | - |
dc.contributor.googleauthor | Park, J H | - |
dc.contributor.googleauthor | Lee, J Y | - |
dc.contributor.googleauthor | Shin, D H | - |
dc.contributor.googleauthor | Kim, H J | - |
dc.contributor.googleauthor | Gu Kong | - |
dc.relation.code | 2011207260 | - |
dc.sector.campus | S | - |
dc.sector.daehak | COLLEGE OF MEDICINE[S] | - |
dc.sector.department | DEPARTMENT OF MEDICINE | - |
dc.identifier.pid | medartisan | - |
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