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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。

基本信息

批准号：
16390576
负责人：
TOTSUKA Yasunori
金额：
$ 9.34万
依托单位：
Hokkaido 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 2005
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-16390576/
关键词：
Oral carcinoma DNA microarray Chemo- and radio- sensitivity Bcl-2 family p53 VEGF-C Bcl-2 口腔扁平上皮がんリンパ節転移 real-time RT-PCR

项目摘要

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

E1AF是一种Ets癌基因家族转录因子，可上调多种MMPs的表达，而细胞外基质降解酶MMP2则不上调。采用氯霉素乙酰转移酶(CAT)比色法检测E1AF是否能上调已知的激活基质金属蛋白酶-2的基质金属蛋白酶-1的表达。通过与E1AF表达载体共转染，在MT1-MMP启动子控制下的CAT报告基因的表达增加了约40倍。实时荧光定量RT-PCR法检测25例舌鳞癌组织中E1AF、MT1-MMPmRNA的表达水平，结果表明E1AF通过将原-MMP2转化为活性MMP2，正向调节Mt1-MMPmRNA的转录，在舌鳞癌的侵袭转移中起重要作用。本文探讨了Bcl2家族基因表达与化疗和放射…作用的关系。更多的食疗。BAX在所有癌组织中的表达均降低。在化疗和放疗耐药的病例中，Bcl2的表达水平较高。采用逆转录-聚合酶链式反应方法检测19例鳞癌和4例癌前病变组织中Ets-1、Ets-2和GnT-V基因的表达，并与正常舌组织进行比较。探讨GnT-V的免疫组织化学检测及其与临床病理特征的关系。实时荧光定量聚合酶链式反应显示，所有癌前病变和鳞癌组织中Ets-1mRNA水平均显著高于正常舌组织。Ets-2和GnT-V mRNAs在鳞癌组织中的表达水平也升高，但在癌前病变组织中的表达水平与正常组织相比无显著差异。GnT-V mRNA水平与Ets-1、Ets-2表达呈正相关(rS=0.7；p&lt；0.01)。Ets-1和GnT-V在鳞癌中的表达与肿瘤侵袭类型和颈淋巴转移呈正相关。相反，Ets-2的表达与这些特征关系不大。这些结果表明，Ets-1在人舌鳞状细胞癌中对GnT-V具有重要的调控作用，并可能通过GnT-V的作用参与舌鳞癌的恶性转化。较少