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Translation research for predicting the prognosis of oral malignant tumors.

Translation research for predicting the prognosis of oral malignant tumors.
预测口腔恶性肿瘤预后的转化研究。
批准号:
16390576
负责人:
TOTSUKA Yasunori
金额:
$9.34万
依托单位:
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
项目状态:
已结题
起止时间:
2004 至 2005

项目摘要

项目成果

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中文摘要
翻译
E1AF是一种ets致癌基因家族转录因子,它已被证明可以上调多种MMPs,而MMP-2(一种有效的细胞外基质降解酶)则不会上调。利用氯霉素乙酰转移酶(CAT)试验研究E1AF是否能够上调MT1-MMP,已知MT1-MMP可激活MMP-2。通过与E1AF表达载体共转染,MT1-MMP启动子控制下CAT报告基因的表达增加了约40倍。对25例舌鳞癌患者进行实时RT-PCR研究,发现E1AF、MT1-MMP mRNA表达水平协同升高。这些结果表明,E1AF正调控MT1-MMP基因的转录,该基因通过将pro-MMP-2转化为active-MMP-2,在舌鳞癌的侵袭转移过程中发挥重要作用。我们研究了Bcl-2家族基因表达与化疗和放疗效果的关系。Bax在所有癌病例中均能降低其表达。在化疗和放疗的耐药病例中观察到高水平的Bcl-2表达。这些结果提示,检查Bcl-2家族基因表达水平可能是术前治疗敏感性的预测因素。应用逆转录聚合酶链反应法分析19例鳞状细胞癌和4例癌前病变组织活检材料中Ets-1、Ets-2和GnT-V mRNA的表达,并与正常舌组织进行比较。观察GnT-V免疫组化检测与临床病理特征的关系。通过实时PCR检测,所有癌前病变和SCC病例与正常舌组织相比,Ets-1 mRNA水平显著升高。Ets-2和GnT-V mrna水平在SCC病例中也有所升高,但与正常组织相比,它们的水平在癌前病变中没有增强。GnT-V mRNA水平与Ets-1和Ets-2表达相关(rs=0.7;p<0.01)。Ets-1和GnT-V在SCC中的表达与肿瘤侵袭方式和颈部淋巴结转移呈正相关。相反,Ets-2的表达与这些特征关系不大。这些结果表明,Ets-1在人舌鳞癌的GnT-V调控中发挥了重要作用,并可能通过GnT-V的作用参与了舌鳞癌的恶性发展。少
英文摘要
E1AF is an ets-oncogene family transcription factor and it has been shown to upregulate multiple MMPs whereas MMP-2, a potent extracellular matrix degrading enzyme, is not upregulated. Chloramphenicol acetyltransferase (CAT) assay was utilized to investigate whether E1AF is able to upregulate MT1-MMP, which is known to activate MMP-2. Expression of the CAT reporter gene under the control of the MT1-MMP promoter was increased approximately 40-fold by co-transfection with the E1AF expression vector. Real-time RT-PCR study was carried out in 25 patients with tongue squamous cell carcinoma, and the mRNA expression level of E1AF,MT1-MMP was synergistically increased.These results indicate that E1AF positively regulates transcription from MT1-MMP genes, which plays an important role in invasion and metastasis of squamous cell carcinoma of the tongue by converting pro-MMP-2 into active-MMP-2.We investigated the relationship between Bcl-2 family gene expression and the effect of chemo- and rad … More iotherapy. Bax was shown to reduce the expression in all carcinoma cases. High expression levels of Bcl-2 were observed in resistant cases for chemo- and radiotherapy. These results suggest that examination of Bcl-2 family gene expression levels would be the predictive factors of sensitivity for preoperative therapies.Ets-1,Ets-2, and GnT-V mRNA expression were analyzed by the reverse transcription-polymerase chain reaction method in biopsy materials of 19 SCC cases and 4 premalignant lesions and compared with the expression levels of normal tongue tissues. Immunohistochemical detection of GnT-V and the relationship between clinico-pathological features were investigated. All premalignant lesions and SCC cases examined showed significantly escalated Ets-1 mRNA levels compered with normal tongue tissues by real-time PCR. Ets-2 and GnT-V mRNAs levels were also increased in SCC cases, but in contrast, their levels were not enhanced in premalignant lesions in comparison to normal tissues. The levels of GnT-V mRNA were correlated with Ets-1 and Ets-2 expression (rs=0.7;p<0.01). Ets-1 and GnT-V expression in SCC were positively associated with the tumor invasive pattern and cervical lymph node metastasis. On the contrary, Ets-2 expression has little relationship with these characteristics. These results suggest that Ets-1 plays a significant role in regulating GnT-V in human tongue squamous cell carcinoma and might be involved in the potential for malignancy via the action of GnT-V. Less
期刊论文(12)
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科研奖励(0)
会议论文
Bcl-2 family遺伝子の発現が口腔扁平上皮がんの術前治療に及ぼす影響
Bcl-2家族基因表达对口腔鳞癌术前治疗的影响
DOI: --
发表时间: 2005
期刊: 北海道歯誌 26
影响因子: --
作者: [浅香雄一郎, 進藤正信, 戸塚靖則, 他]
通讯作者: 他
EIAF exression is closely correlated with malignant phenotype of tongue squamous cell carcinoma through activation of MT1-MMP gene promoters.
EIAF表达通过MT1-MMP基因启动子的激活与舌鳞状细胞癌的恶性表型密切相关。
DOI: --
发表时间: 2005
期刊: Oncol Rep 13
影响因子: --
作者: [Izumiyama Y, Ohiro Y, Higashiono F, Totsuka Y, Shindoh M et al.]
通讯作者: Shindoh M et al.
E1AF exression is closely correlated with malignant phenotype of tongue squamous cell carcinoma through activation of MT1-MMP gene promoters.
E1AF表达通过激活MT1-MMP基因启动子与舌鳞状细胞癌的恶性表型密切相关。
DOI: --
发表时间: 2005
期刊: Oncol Rep 13
影响因子: --
作者: [Izumiyama Y, Ohiro Y, Higashiono F, Totsuka Y, Shindoh M et al.]
通讯作者: Shindoh M et al.
ElAF expression is closely correlated with malignant phenotype of tongue squamous cell carcinoma through activation of MT1-MMP gene promoters.
ElAF表达通过MT1-MMP基因启动子的激活与舌鳞状细胞癌的恶性表型密切相关。
DOI: --
发表时间: 2005
期刊: Oncol Rep 13
影响因子: --
作者: [Izumiyama Y, Higashino F, Totsuka Y, Shindoh M et al.]
通讯作者: Shindoh M et al.
共 9 条
    Basic research for oral cancer diagnosis estimated by HuR export
    • 批准号:
      22659360
    • 项目类别:
      Grant-in-Aid for Challenging Exploratory Research
    • 资助金额:
      $2.05万
    • 财政年份:
      2010
    • 负责人:
      TOTSUKA Yasunori
    • 依托单位:
    Exploitation of gene-targeting therapy based on the cellular and biological features of oral-carcinoma stem cell and tumor microenvironment.
    • 批准号:
      20249079
    • 项目类别:
      Grant-in-Aid for Scientific Research (A)
    • 资助金额:
      $19.47万
    • 财政年份:
      2008
    • 负责人:
      TOTSUKA Yasunori
    • 依托单位:
    Gene Targeting Therapy against tumor endothelial cells
    • 批准号:
      18390530
    • 项目类别:
      Grant-in-Aid for Scientific Research (B)
    • 资助金额:
      $10.71万
    • 财政年份:
      2006
    • 负责人:
      TOTSUKA Yasunori
    • 依托单位:
    Induction of apoptosis in oral squamous cell carcinoma by activating caspase
    • 批准号:
      13557172
    • 项目类别:
      Grant-in-Aid for Scientific Research (B)
    • 资助金额:
      $8.9万
    • 财政年份:
      2001
    • 负责人:
      TOTSUKA Yasunori
    • 依托单位:
    海外基金