Genome-wide allelotype analysis of sporadic primary nasopharyngeal carcinoma from southern China.

Shao, Jian Yong; Wang, Huiyun; Huang, Xiaoming; Qian, Feng; Huang, Ping; Feng, Bing‐Jian; Huang, Lixi; Yu, Xinjuan; Li, Jingtian; Hu, Li–Fu; Ernberg, Ingemar; Zeng, Yi-Xin

doi:10.3892/ijo.17.6.1267

Cited by 51 publications

(60 citation statements)

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“…In the revised Knudson two-hit theory, 14 besides deletion and mutation, DNA methylation was included as an alternative mechanism for the inactivation of tumor suppressor genes. So far, no evidence of loss of heterozygosity (LOH) on 20p was reported in NPC 15,16 and no somatic mutations other than polymorphism of RASSF2A could be found in human cancers. The methylation of RASSF2A in NPC seems to be bi-allelic, since a methylation degree of 60-100% was observed for most of the CpG pairs in the RASSF2A-silenced NPC cell lines CNE1 and CNE2.…”

Section: Discussionmentioning

confidence: 99%

Inactivation of RASSF2A by promoter methylation correlates with lymph node metastasis in nasopharyngeal carcinoma

Zhang

Sun

Van

et al. 2006

Intl Journal of Cancer

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RASSF2 can bind directly to K-Ras and function as a negative effector of Ras protein. RASSF2A is the only isoform of RASSF2 that contains CpG islands in its promoter and it has been reported to be inactivated by its promoter methylation in several human cancers. In the present study, we investigated the correlation of RASSF2A expression with its promoter methylation in nasopharyngeal carcinoma (NPC). Expression of RASSF2A was downregulated in 80% (4/5) of NPC cell lines. Decreased RASSF2A expression was also observed in NPC primary tumors compared with normal nasopharyngeal epithelia. Promoter methylation of RASSF2A could be detected in all the RASSF2A-silenced cell lines (4/5) of the NPC cell lines and 50.9% (27/53) of primary tumors, but not in any of the normal epithelia. RASSF2A-methylated cases showed a significantly lower level of RASSF2A expression than unmethylated cases. Loss of RASSF2A expression can be greatly restored by the methyltransferase inhibitor 5-aza-dC in NPC cell lines. In addition, patients with methylated RASSF2A presented a higher frequency of lymph node metastasis (p < 0.05). Ectopic expression of RASSF2A in RASSF2A-silenced and -methylated NPC cell line CNE2 shows that RASSF2A could inhibit cell cycle progression, colony formation and cell migration, which provided further evidence that RASSF2A is a candidate tumor suppressor gene. In conclusion, RASSF2A, a candidate tumor suppressor gene (TSG), is frequently inactivated by its promoter methylation and this aberrant methylation correlates with lymph node metastasis in NPC. ' 2006 Wiley-Liss, Inc.

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Section: Discussionmentioning

confidence: 99%

Inactivation of RASSF2A by promoter methylation correlates with lymph node metastasis in nasopharyngeal carcinoma

Zhang

Sun

Van

et al. 2006

Intl Journal of Cancer

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“…[28][29][30] Our previous studies and those of others have shown that the NPC susceptibility locus was mapped to a 13.6-cM region of chromosome 3p21.31-21.2, a site of frequent loss of heterozygosity in NPC. 2,[31][32][33][34][35][36] In our study, we characterized the expression profiles of 288 cDNA clones from chromosome 3p21 using a custom-made cDNA microarray of 22 human NPC and 10 nontumor nasopharyngeal epithelial tissues. We found that the expression of genes for LTF, TU3A, dystroglycan1 and FLJ34969 was downregulated, while those for the glutamate receptor metabotropic 2 and IL-17 receptor B were upregulated in NPC.…”

Section: Discussionmentioning

confidence: 99%

Lactotransferrin: A candidate tumor suppressor—Deficient expression in human nasopharyngeal carcinoma and inhibition of NPC cell proliferation by modulating the mitogen‐activated protein kinase pathway

Zhou

Zeng

Zhang

et al. 2008

Intl Journal of Cancer

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Lactotransferrin (LTF) has been shown to regulate tumorogenesis. However, little is known about the role of LTF in regulating the development of human nasopharyngeal carcinoma (NPC). The aim of our study was to investigate whether LTF could regulate the development of NPC by characterizing the pattern of LTF expression in human NPC tissues using cDNA and tissue microarrays. Loss of LTF expression was observed in a significantly higher frequency of NPC tissues compared to that in nontumor nasopharyngeal epithelial tissues. While 61.25% of NPC tissues at the T1/T2 stage were positive for LTF expression, only 40.82% of NPC at the T3/T4 stage were stained by anti-LTF. Similarly, 41.58% of NPC with local lymph node metastasis displayed LTF expression, a value significantly lower than the 46.36% in primary tumors (p < 0.05). These findings suggest that LTF may negatively regulate the development and metastasis of NPC in vivo. Furthermore, overexpression of or treatment with LTF inhibited the proliferation of NPC cells and promoted cell cycle arrest at the G 0 /G 1 phase in vitro. While LTF treatment downregulated expression of cyclin D1 and phosphorylation of retinoblastoma protein (Rb), expression of p21 and p27 in 5-8F NPC cells was enhanced. Moreover, LTF treatment modulated the mitogen-activated protein kinase (MAPK) pathway, but did not affect p53 and STAT3 expression in 5-8F NPC cells. Thus LTF is likely to be a candidate tumor suppressor and downregulates the development of NPC by inhibiting NPC proliferation through induction of cell cycle arrest and modulation of the MAPK signaling pathway. Therefore, our findings provide new insights in understanding the mechanism(s) underlying the action of LTF in regulating the development of human NPC.

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“…Until 1990, radiotherapy was the standard treatment for all stages of NPC (8). Despite significant progress in intensity-modulated radiation therapy and other types of therapy such as surgery and molecular targeted therapy, the outcomes for the patients remain disappointing, with five-year survival rates of 34-52% (9).…”

Section: Introductionmentioning

confidence: 99%

Embelin prevents LMP1-induced TRAIL resistance via inhibition of XIAP in nasopharyngeal carcinoma cells

Yang¹,

Li²,

Yang³

et al. 2016

Oncology Letters

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Abstract. The tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) selectively induces apoptosis in the majority of tumor cells, whilst sparing normal cells. However, the potential use of TRAIL in the treatment of cancer is limited by the inevitable emergence of drug resistance. The present study reports the upregulation of latent membrane protein 1 (LMP1)-induced TRAIL resistance via the enhanced expression of X-linked inhibitor of apoptosis protein (XIAP) in nasopharyngeal carcinoma (NPC) cells. LMP1-positive NPC cells were indicated to be more sensitive to TRAIL compared with LMP1-negative NPC cells in three NPC cell lines. CNE-1 is a LMP1-negative NPC cell line that was transfected with pGL6-LMP1; following which, sensitivity to TRAIL decreased. LMP1-induced TRAIL resistance was associated with the decreased cleavage of caspase-8,-3 and -9, BH3 interacting domain death agonist (Bid) and mitochondrial depolarization, without any effects on the expression of the death receptors, B-cell lymphoma (Bcl)-2 and Bcl-extra long. Knockdown of XIAP with small interfering RNA increased caspase-3 and -9 and Bid cleavage, and prevented LMP1-induced TRAIL resistance. Furthermore, embelin, the inhibitor of XIAP, prevented LMP1-induced TRAIL resistance in the Epstein-Barr virus (EBV)-positive CNE-1-LMP1 and C666-1 NPC cell lines. However, embelin did not enhance TRAIL-induced apoptosis in NP-69, which was used as a benign nasopharyngeal epithelial cell line. These data show that LMP1 inhibits TRAIL-mediated apoptosis by upregulation of XIAP. Embelin may be used in an efficacious and safe manner to prevent LMP1-induced TRAIL resistance. The present study may have implications for the development and validation of novel strategies to prevent TRAIL resistance in EBV-positive NPC.

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Genome-wide allelotype analysis of sporadic primary nasopharyngeal carcinoma from southern China.

Cited by 51 publications

References 0 publications

Inactivation of RASSF2A by promoter methylation correlates with lymph node metastasis in nasopharyngeal carcinoma

Inactivation of RASSF2A by promoter methylation correlates with lymph node metastasis in nasopharyngeal carcinoma

Lactotransferrin: A candidate tumor suppressor—Deficient expression in human nasopharyngeal carcinoma and inhibition of NPC cell proliferation by modulating the mitogen‐activated protein kinase pathway

Embelin prevents LMP1-induced TRAIL resistance via inhibition of XIAP in nasopharyngeal carcinoma cells

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