A Role of HMGIC in Squamous Carcinoma Cells of The Oral Cavity

HMGIC 在口腔鳞状细胞癌中的作用

• 批准号: 16591898
• 负责人: IMAI Kazushi
• 金额: $ 2.24万
• 依托单位: The Nippon Dental University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 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/en/grant/KAKENHI-PROJECT-16591898/
• 关键词: Oral carcinomas; HMGA2; Transcription factor; sChIP; SChIP

In a previous study, we showed that expression of a transcription factor-high mobility group protein (HMGIC/HMGA2), which plays a critical role in differentiation and growth of un-differentiated mesenchymal cells during development, is frequently observed in oral carcinomas and associates with 5-year survival rate of patients suffered from the disease. Understanding a role of HMGIC expression should expand knowledge of a molecular mechanism(s) of cancer progression. In this end, we developed a novel high-throughput analysis, named sChIP, to unveil HMGA2 target genes. We identified approx. 100 genes, and focused on 5 different genes, which are expected to be involved in the progression of oral carcinomas. RT-PCR showed that expression of these 5 genes were negligible in differentiated HaCaT keratinocytes but upregulated in undifferentiated HaCaT cells. In addition, oral carcinoma cells without HMGIC expression (KOSC3, Ho1u1) did not express these 5 genes in contrast to the expression in carcinoma cells expressing HMGIC gene (HOC313, TSU). To understand the transcriptional activity of HMGIC, we are currently investigating it by a reporter assay using luciferase system. Expression of HMGIC target genes in keratinocytes isolated from Hmgic-null mice is also under investigation. We will develop carcinoma cell lines which are specifically knock-downed HMGA2 gene by RNAi, and analyze a direct role of HMGIC and the target genes on tumorgenisity, and invasiveness, metastatic potential and phenotypic alterations of carcinoma cells.

在先前的研究中，我们发现，在发育过程中未分化间充质细胞的分化和生长中起关键作用的转录因子-高迁移率族蛋白（HMGIC/HMGA 2）的表达经常在口腔癌中观察到，并与患有该疾病的患者的5年生存率相关。了解HMGIC表达的作用将扩大对癌症进展的分子机制的认识。为此，我们开发了一种新的高通量分析方法，命名为sChIP，以揭示HMGA 2靶基因。我们确定了接近。100个基因，并集中在5个不同的基因，这是预期参与口腔癌的进展。RT-PCR结果显示，这5个基因在分化的HaCaT角质形成细胞中的表达可以忽略不计，但在未分化的HaCaT细胞中上调。另外，与表达HMGIC基因的癌细胞（HOC 313，大津）中的表达相反，不表达HMGIC的口腔癌细胞（KOSC 3，Ho 1u 1）不表达这5种基因。为了了解HMGIC的转录活性，我们目前正在使用荧光素酶系统通过报告基因测定来研究它。HMGIC靶基因在分离自HMGIC缺失小鼠的角质形成细胞中的表达也在研究中。本研究拟建立特异性RNAi敲除HMGA 2基因的肿瘤细胞系，并分析HMGIC及其靶基因对肿瘤发生、侵袭力、转移潜能和肿瘤细胞表型改变的直接作用。

项目成果

Expression of SIP1 in oral squamous cell carcinomas: implications for E-cadherin expression and tumor progression.

• DOI: 10.3892/ijo.27.6.1535
• 发表时间: 2005-12
• 期刊: International journal of oncology
• 影响因子: 5.2
• 作者: G. Maeda;T. Chiba;M. Okazaki;T. Satoh;Y. Taya;T. Aoba;K. Kato;S. Kawashiri;K. Imai

Ectopic activation of mesenchyme-specific genes induce the epithelial mesenchymal transition in oral cancer.

间充质特异性基因的异位激活诱导口腔癌的上皮间质转化。

• 发表时间: 2005
• 期刊: Res.Adv.in Cancer 5
• 作者: M.Nasu;F.Mitsuhashi;T.Yosue et al.;Kazushi Imai
• 通讯作者: Kazushi Imai

Ectopic activation of mesenchyme-specific genes induce the epithelial-mesenchymal transition in oral cancer, in "Research Advances in Cancer"

间充质特异性基因的异位激活诱导口腔癌的上皮间充质转化，在“癌症研究进展”中

• 发表时间: 2005
• 作者: Aida Y;Maeno M;Suzuki N;Shiratsuchi H;Motohashi M;Matsumura H.;Kazushi Imai
• 通讯作者: Kazushi Imai

転写因子の標的遺伝子検出方法

一种转录因子靶基因的检测方法

• 发表时间: 2005

Ectopic activation of mesenchyme-specific genes induce the epithelial-mesenchymal transition in oral cancer.

间充质特异性基因的异位激活诱导口腔癌的上皮-间质转化。

• 发表时间: 2005
• 期刊: Res. Adv. in Cancer 5
• 作者: Fujisaki K;Tanabe N;Suzuki N;Kawato T;Takeichi O;Tsuzukibashi O;Makimura M;Ito K;Maeno M;Koichiro Ueda;Kazushi Imai
• 通讯作者: Kazushi Imai