Dataset Information

HLA associations with nasopharyngeal carcinoma.

ABSTRACT: Several associations have been described between the frequency of human leukocyte antigen (HLA) class I genes in certain populations and the risk of developing nasopharyngeal carcinoma (NPC). Associations between ethnic background and geographic distribution, and relative disease incidence have been reported. Populations in geographical areas at higher risk of developing NPC display HLA distribution patterns different and sometimes opposite from areas of low incidence, whereas populations in areas with intermediate incidence display a totally independent pattern. Two main reasons may explain this association between HLA phenotype distribution and the risk of developing NPC in various populations. First, given the fact that expression of Epstein-Barr Virus (EBV) proteins by cancer cells is tightly linked with NPC development, HLA may influence the development of NPC by modulating the expression of EBV proteins. This explanation is, however, based primarily on theoretical assumptions given that no clear definition of HLA binding pattern of EBV epitopes has been directly shown to significantly alter the recognition of EBV proteins and the risk of developing the disease. Alternatively, HLA may represent a genetic marker flagging the presence of a NPC predisposition locus in close linkage disequilibrium with the HLA class I region. A critical review of known HLA associations in various geographical areas and their interpretation will be presented in this review.

SUBMITTER: Li X

PROVIDER: S-EPMC3407690 | biostudies-literature | 2009 Aug

REPOSITORIES: biostudies-literature

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HLA associations with nasopharyngeal carcinoma.

Li Xin X Fasano Ross R Wang Ena E Yao Kai-Tai KT Marincola Francesco M FM

Current molecular medicine 20090801 6

Several associations have been described between the frequency of human leukocyte antigen (HLA) class I genes in certain populations and the risk of developing nasopharyngeal carcinoma (NPC). Associations between ethnic background and geographic distribution, and relative disease incidence have been reported. Populations in geographical areas at higher risk of developing NPC display HLA distribution patterns different and sometimes opposite from areas of low incidence, whereas populations in are ...[more]

PMID: 19689302

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Project description: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.

Dataset Information

HLA associations with nasopharyngeal carcinoma.

Publications

HLA associations with nasopharyngeal carcinoma.

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