Anti-angiogenic pathway associations of the 3p21.3 mapped BLU gene in nasopharyngeal carcinoma

Autor: Z. B. Feng, Arthur Kl Cheung, Hong Lok Lung, Yue Cheng, S. Chen, Zhe Zhang, R. Kan, Josephine Mun Yee Ko, Kevin C. Chan, E. Tung, Xin Yuan Guan, Eric J. Stanbridge, Dora L.W. Kwong, Wing Lung Yau, D. Z. Luo, R. L.K.Y. Ho, Maria Li Lung
Jazyk: angličtina
Rok vydání: 2014
Předmět:
Male
Vascular Endothelial Growth Factor A
Cancer Research
Angiogenesis
Nude
Thrombospondin 1
Mice
Cell Movement
Gene expression
Tumor Microenvironment
Cells
Cultured
Regulation of gene expression
Tube formation
Heterologous
Cultured
Tumor
Nasopharyngeal Carcinoma
Neovascularization
Pathologic
Blotting
Reverse Transcriptase Polymerase Chain Reaction
Chromosome Mapping
Immunohistochemistry
Gene Expression Regulation
Neoplastic
Pair 3
Original Article
Female
Chromosomes
Human
Pair 3
Western
Human
Signal Transduction
Cells
Oncology and Carcinogenesis
Clinical Sciences
Blotting
Western
Transplantation
Heterologous
Nasopharyngeal neoplasm
Down-Regulation
Mice
Nude
Biology
Chromosomes
Cell Line
Cell Line
Tumor
Genetics
medicine
otorhinolaryngologic diseases
Animals
Humans
Oncology & Carcinogenesis
Molecular Biology
Neovascularization
Pathologic
Transplantation
Neoplastic
Tumor microenvironment
Tumor Suppressor Proteins
Carcinoma
Nasopharyngeal Neoplasms
medicine.disease
Molecular biology
Matrix Metalloproteinases
stomatognathic diseases
Cytoskeletal Proteins
Gene Expression Regulation
Nasopharyngeal carcinoma
Cell culture
Cancer research
Zdroj: Oncogene
Oncogene, vol 34, iss 32
Cheng, Y; Ho, RLKY; Chan, KC; Kan, R; Tung, E; Lung, HL; et al.(2014). Anti-angiogenic pathway associations of the 3p21.3 mapped BLU gene in nasopharyngeal carcinoma. Oncogene. doi: 10.1038/onc.2014.353. UC Irvine: Retrieved from: http://www.escholarship.org/uc/item/70q7r6pc
ISSN: 1476-5594
0950-9232
DOI: 10.1038/onc.2014.353.
Popis: © 2014 Macmillan Publishers Limited Zinc-finger, MYND-type containing 10 (ZMYND10), or more commonly called BLU, expression is frequently downregulated in nasopharyngeal carcinoma (NPC) and many other tumors due to promoter hypermethylation. Functional evidence shows that the BLU gene inhibits tumor growth in animal assays, but the detailed molecular mechanism responsible for this is still not well understood. In current studies, we find that 93.5% of early-stage primary NPC tumors show downregulated BLU expression. Using a PCR array, overexpression of the BLU gene was correlated to the angiogenesis network in NPC cells. Moreover, expression changes of the MMP family, VEGF and TSP1, were often detected in different stages of NPC, suggesting the possibility that BLU may be directly involved in the microenvironment and anti-angiogenic activity in NPC development. Compared with vector-alone control cells, BLU stable transfectants, derived from poorly-differentiated NPC HONE1 cells, suppress VEGF165, VEGF189 and TSP1 expression at both the RNA and protein levels, and significantly reduce the secreted VEGF protein in these cells, reflecting an unknown regulatory mechanism mediated by the BLU gene in NPC. Cells expressing BLU inhibited cellular invasion, migration and tube formation. These in vitro results were further confirmed by in vivo tumor suppression and a matrigel plug angiogenesis assay in nude mice. Tube-forming ability was clearly inhibited, when the BLU gene is expressed in these cells. Up to 70–90% of injected tumor cells expressing increased exogenous BLU underwent cell death in animal assays. Overexpressed BLU only inhibited VEGF165 expression in differentiated squamous NPC HK1 cells, but also showed an anti-angiogenic effect in the animal assay, revealing a complicated mechanism regulating angiogenesis and the microenvironment in different NPC cell lines. Results of these studies indicate that alteration of BLU gene expression influences anti-angiogenesis pathways and is important for the development of NPC.Oncogene advance online publication, 27 October 2014; doi:10.1038/onc.2014.353.
Databáze: OpenAIRE
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