Identification of Metastasis-related Gene in Oral Cancer

口腔癌转移相关基因的鉴定

• 批准号: 6787731
• 负责人: ZHUO Georgia CHEN
• 金额: $ 15.3万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-08-06 至 2006-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6787731
• 关键词: cell line; clinical research; functional /structural genomics; gene expression; genetic mapping; informatics; laboratory mouse; metastasis; microarray technology; molecular biology information system; neoplasm /cancer genetics; northern blottings; oral pharyngeal neoplasm; squamous cell carcinoma; transfection; western blottings

DESCRIPTION (provided by applicant): In the study proposed here, the cDNA microarray technique in combination with statistical and computational methods for whole-genome functional analysis will be used to identify metastasis-related genes in oral squamous cell carcinoma (SCC) in a novel lymph nodal metastatic mouse model. As a result of a unique feature of the mouse model, the abundance of testing samples, and the powerful statistical methods that will be used for data analysis, this study promises to generate significant data and lead to further studies that will increase understanding of the expression of metastatic genes. It is an appropriate application for an Exploratory/Developmental Research Grant as defined in the Purpose section of the program announcement. To study the metastasis of oral SCC, we recently established highly metastatic oral SCC cell lines from a population of poorly metastatic oral SCC cells through in vivo selection using a modified floor-of-mouth (FOM) human tumor animal model. We compared the gene expression in 12 highly metastatic cell lines with their poorly metastatic parental cells using cDNA microarray analysis, rapid analysis of gene expression (RAGE), and northern and western blot analyses. The preliminary experiments revealed the existence of several genes and expressed sequence tags whose expressions were significantly altered in the selected metastatic cell lines. Based on our preliminary findings, we posit that the nodal metastatic mouse model in combination with cDNA microarray analysis can be used to identify alterations of gene expressions that are responsible for enhancing the metastatic potential of oral SCC and for facilitating the migration of SCC cells to and the growth in cervical lymph nodes. There are two Specific Aims in the study. The first is to identify the genes that are up- and down-regulated in highly metastatic oral SCC. DNA microarray and data mining methods such as cluster analysis and feature selection will be used to compare gene expression in highly metastatic primary tumor cells with that in poorly metastatic primary tumor cells and in lymph node metastases. RAGE and northern blot analysis will be done in both oral SCC cell lines and clinical specimens to further confirm the result from DNA microarray analysis. The second is to confirm the effect of differentially expressed genes on the metastatic phenotype of oral SCC cells. The cDNAs of the genes of interest will be inserted into a eukaryotic expression vector in either a sense or antisense format and transfected into either poorly metastatic parental cells or their highly metastatic derivatives. The transfectant will be examined using in vitro and in vivo assays to determine the roles of these genes in metastasis. This study will help to identify genes whose expression levels are crucial for metastatic behaviors. The findings from this project will serve as the basis for an NIH R01 grant application.

描述（由申请人提供）：在此提出的研究中，cDNA微阵列技术与全基因组功能分析的统计和计算方法相结合，将用于以一种新颖的方式鉴定口腔鳞状细胞癌（SCC）中的转移相关基因。淋巴结转移小鼠模型。由于小鼠模型的独特特征、丰富的测试样本以及用于数据分析的强大统计方法，这项研究有望产生重要的数据并导致进一步的研究，从而增加对表达的理解转移基因。这是项目公告目的部分中定义的探索性/发展性研究补助金的适当申请。为了研究口腔鳞状细胞癌的转移，我们最近使用改良的口底（FOM）人类肿瘤动物模型通过体内选择从一群低转移性口腔鳞状细胞癌细胞中建立了高转移性口腔鳞状细胞癌细胞系。我们使用 cDNA 微阵列分析、基因表达快速分析 (RAGE) 以及 Northern 和 Western blot 分析，比较了 12 个高转移细胞系与其低转移亲本细胞的基因表达。初步实验揭示了一些基因和表达序列标签的存在，其表达在选定的转移细胞系中显着改变。根据我们的初步研究结果，我们假设结节转移小鼠模型与 cDNA 微阵列分析相结合，可用于识别基因表达的改变，这些改变负责增强口腔鳞状细胞癌的转移潜力，并促进鳞状细胞癌细胞迁移至口腔鳞状细胞癌和口腔鳞状细胞癌。颈部淋巴结的生长。该研究有两个具体目标。首先是确定在高度转移性口腔鳞状细胞癌中上调和下调的基因。 DNA微阵列和数据挖掘方法（例如聚类分析和特征选择）将用于比较高转移原发肿瘤细胞与低转移原发肿瘤细胞和淋巴结转移中的基因表达。将在口腔 SCC 细胞系和临床标本中进行 RAGE 和 Northern 印迹分析，以进一步确认 DNA 微阵列分析的结果。二是确认差异表达基因对口腔SCC细胞转移表型的影响。目的基因的 cDNA 将以有义或反义形式插入真核表达载体中，并转染至低转移性亲代细胞或其高转移性衍生物中。将使用体外和体内测定来检查转染子，以确定这些基因在转移中的作用。这项研究将有助于识别其表达水平对转移行为至关重要的基因。该项目的研究结果将作为 NIH R01 拨款申请的基础。

项目成果

Restoration of caveolin-1 expression suppresses growth and metastasis of head and neck squamous cell carcinoma.

Caveolin-1 表达的恢复可抑制头颈鳞状细胞癌的生长和转移。

• 发表时间: 2008-11-18
• 影响因子: 8.8
• 作者: Zhang, H;Su, L;Muller, S;Tighiouart, M;Xu, Z;Zhang, X;Shin, H J C;Hunt, J;Sun, S;Shin, D M;Chen, Z G
• 通讯作者: Chen, Z G

Distinctive E-cadherin and epidermal growth factor receptor expression in metastatic and nonmetastatic head and neck squamous cell carcinoma: predictive and prognostic correlation.

转移性和非转移性头颈鳞状细胞癌中独特的 E-钙粘蛋白和表皮生长因子受体表达：预测和预后相关性。

• 发表时间: 2008-07-01
• 影响因子: 6.2
• 作者: Muller, Susan;Su, Ling;Tighiouart, Mourad;Saba, Nabil;Zhang, Hongzheng;Shin, Dong M;Chen, Zhuo Georgia
• 通讯作者: Chen, Zhuo Georgia

CXC chemokine receptor-4 antagonist blocks both growth of primary tumor and metastasis of head and neck cancer in xenograft mouse models.

CXC 趋化因子受体 4 拮抗剂可阻断异种移植小鼠模型中原发肿瘤的生长和头颈癌的转移。

• 发表时间: 2007-08-01
• 影响因子: 11.2
• 作者: Yoon, Younghyoun;Liang, Zhongxing;Zhang, Xin;Choe, Mison;Zhu, Aizhi;Cho, Heidi T;Shin, Dong M;Goodman, Mark M;Chen, Zhuo Georgia;Shim, Hyunsuk
• 通讯作者: Shim, Hyunsuk

Human papillomavirus 16 oncoprotein regulates the translocation of β-catenin via the activation of epidermal growth factor receptor.

人乳头瘤病毒 16 癌蛋白通过表皮生长因子受体的激活调节 β-连环蛋白的易位。

• 发表时间: 2015-01-15
• 影响因子: 6.2
• 作者: Hu, Zhongliang;Müller, Susan;Qian, Guoqing;Xu, Jing;Kim, Sungjin;Chen, Zhengjia;Jiang, Ning;Wang, Dongsheng;Zhang, Hongzheng;Saba, Nabil F;Shin, Dong M;Chen, Zhuo Georgia
• 通讯作者: Chen, Zhuo Georgia