The relationship between single nucleotide polymorphism of matrix metallopraeinase-1 and metastasis of nasopharyngeal carcinoma.

基质金属蛋白酶1单核苷酸多态性与鼻咽癌转移的关系

• 批准号: 16390487
• 负责人: FURUKAWA Mitsuru
• 金额: $ 8.9万
• 依托单位: Kanazawa University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2004
• 资助国家: 日本
• 起止时间: 2004 至 2006
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-16390487/
• 关键词: NPC; EBV; SNP; LMP1; MMP1; Ets-1; 上咽頭がん; ets1

The Epstein-Barr Virus (EBV) latent membrane protein 1 (LMP1) has a significant role in several malignancies, including nasopharyngeal carcinoma (NPC). LMP1 is principal onco-protein, and we have shown that it also induces a set of factors that mediated invasion, angiogenesis and metastasis. Matrix metarolloproteinase-1 (MMP1) is also involved in several malignancies. A single guanine insertion polymorphism (2G) in the MMP1 promoter creates an Ets binding site that causes high levels of transcription and correlates with risk for some malignancies. Here, we evaluate the impact of this 2G insertion type on NPC. We genotyped 44 Japanese and 39 Taiwanese NPC patients, as well as 58 Japanese and 23 Taiwanese healthy controls. The proportion of 2G homozybotes was higher in the NPC groups than controls (Japanese : p= 0.02, odds ratio (OR) =2.49 ; Taiwanese : p= 0.02, OR= 3.66). An analysis of overall survival rates in the patients with NPC, and the 1G/1G genotype disclosed a favorable prognosis (5-year survival rate = 100%, P= 0.04). Multivariate analysis showed that 1G/1G has independent prognostic significance. We also examined whether LMP1 enhances MMP1 expression in epithelial cells in culture. LMP1-transfected cells with 2G/2G genotype expressed MMP1, which was abolished by activator protein-1(AP1) dominant-negative (DN) and Ets-DN. LMP1 also induced active MMP3, which can cleave latent MMP1, and AP-1 DN-and Ets-DN suppressed the MMP3 expression. These results suggest that LMP1-induced MMP1 and MMP3 are closely linked and show that LMP1 activates MMP1 via an Ets binding site formed by 2G, which is a candidate marker for both risk and prognosis of NPC.

EB病毒（EBV）潜伏膜蛋白1（LMP 1）在包括鼻咽癌（NPC）在内的多种恶性肿瘤中具有重要作用。LMP 1是主要的癌蛋白，我们已经发现它还诱导一系列介导侵袭、血管生成和转移的因子。基质金属蛋白酶-1（MMP 1）也参与了几种恶性肿瘤。MMP 1启动子中的单个鸟嘌呤插入多态性（2G）产生Ets结合位点，该位点导致高水平转录并与某些恶性肿瘤的风险相关。在这里，我们评估这种2G插入类型对NPC的影响。我们对44名日本和39名台湾NPC患者以及58名日本和23名台湾健康对照进行了基因分型。NPC组2G纯合子的比例高于对照组（日本人：p= 0.02，OR =2.49 ;台湾人：p= 0.02，OR= 3.66）。鼻咽癌患者的总生存率分析显示，1G/1G基因型预后良好（5年生存率= 100%，P= 0.04）。多因素分析显示1G/1G具有独立的预后意义。我们还研究了LMP 1是否增强培养的上皮细胞中MMP 1的表达。2G/2G基因型的LMP 1转染细胞表达MMP 1，激活蛋白1（AP 1）显性阴性（DN）和Ets-DN可阻断MMP 1的表达。LMP 1还可诱导MMP 3的活化，使MMP 3裂解潜伏的MMP 1，AP-1 DN-1和Ets-DN可抑制MMP 3的表达。这些结果表明，LMP 1诱导的MMP 1和MMP 3是密切相关的，并表明LMP 1通过2G形成的Ets结合位点激活MMP 1，这是NPC风险和预后的候选标志物。

项目成果

Metastasizing mixed tumour of the parotid gland presenting as multiple lung metastases.

腮腺转移性混合瘤表现为多发性肺转移。

• 发表时间: 2004
• 期刊: J Laryngol Otol. 118
• 作者: Tonchev AB;Yamashima T;Sawamoto K;Okano H.;Yoshizaki T et al.
• 通讯作者: Yoshizaki T et al.

Diagnostic value of serum EBV-DNA quantification and antibody to viral capsid antigen in nasopharyngeal carcinoma patients

• DOI: 10.1111/j.1349-7006.2004.tb03241.x
• 发表时间: 2004-06-01
• 期刊: CANCER SCIENCE
• 影响因子: 5.7
• 作者: Kondo, S;Horikawa, T;Yoshizaki, T
• 通讯作者: Yoshizaki, T

Oncogenic role of Epstein-Barr virus-encoded small RNAs(EBERs)in nasopharyngeal carcinoma.

Epstein-Barr 病毒编码的小 RNA (EBER) 在鼻咽癌中的致癌作用。

• 发表时间: 2007
• 期刊: Auris Nasus Larynx 34・1
• 作者: Yoshizaki T;Endo K;et. al.
• 通讯作者: et. al.

EBV latent membrane protein 1 induces synthesis of Hypoxia-inducible factor 1 α through Siah1-mediated down-regulation of prolyl hydroxylases 1 and 3 in nasopharyngeal epithelial cells.

EBV潜伏膜蛋白1通过Siah1介导的鼻咽上皮细胞中脯氨酰羟化酶1和3的下调来诱导缺氧诱导因子1α的合成。

• 发表时间: 2006
• 期刊: Pagano. Cancer Res 66(20)
• 作者: Satoru Kondo;So Young Seo;Tomokazu Yoshizaki;Naohiro Wakisaka;Mitsuru Furukawa;Irene Joab;Kyung Lib Jang;Joseph S.
• 通讯作者: Joseph S.

耳鼻咽喉科診療とウイルス学

耳鼻喉科和病毒学

• 发表时间: 2006
• 期刊: 耳鼻咽喉科・頭頸部外科 78(1)
• 作者: Hato N;Furuta Y;et al.;古川 仭
• 通讯作者: 古川 仭