Molecular analysis of 4NQO-induced rat tongue cancers using cDNA microarrays - for a purpose of clinical application

使用 cDNA 微阵列对 4NQO 诱导的大鼠舌癌进行分子分析 - 用于临床应用

• 批准号: 12470399
• 负责人: SEMBA Ichiro
• 金额: $ 9.02万
• 依托单位: Kagoshima University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-12470399/
• 关键词: 4NQO-induced rat tongue cancer; Experimental model of tongue cancer; Tongue cancer susceptibility gen; cDNA microarray; Signal analysis; Global gene expression; Ratio of the signals of cancer to normal; NQO1-gene; 舌癌抵抗性遺伝子; コンジェニックラット; 主要組織適合抗原遺

Here we report that use of cDNA microarrays to measure global patterns of gene expression in 4-nitroquinoline 1-oxide (4NQO)-induced rat tongue carcinoma tissue. Measurements of gene expression have been the basis for molecular differentiation of two strains of the rats, highly susceptible Dark-Agouti (DA) rat and poorly susceptible Wistar/Furth (WF) rat (Kitano et al, Jpn J Cancer Res 83, 845-50, 1992 ; Kitano et al, Jpn J Cancer Res 87, 1097-101, 1996). For quantification of the gene expression, fluorescence derived from microarrays hybridized in parallel to control (Cy3-labelled) and 4-nitroquinoline 1-oxide-induced rat tongue cancer (Cy5-labelled) cDNA samples of the two strains of rats were overlayed and analyzed. The expression factor --- evaluated from quadruplicate hybridization --- was determined as a mean value according to the ratios of the Cy5/Cy3 signal intensities. More than 3-fold increases or decreases of the gene expression ratios were regarded as relevant in this experiment. The genes which were up-regulated and down-regulated in a 4NQO-induced tongue cancer (15mm in the diameter) of a DA rat was 337 and 220, respectively, and another 4NQO-induced tongue cancer (5mm in the diameter) developed in a WF rat was 182 and 81, respectively. Regarding the genes previously described as the candidates for QTLs involved in susceptibility of tongue carcinogenesis in the rat (Tanuma et al, Cancer Res 58, 1660-4, 1998 ; Tanuma et al, Jpn J Cancer Res 92, 610-6, 2001 ; Tanuma et al, Int J Cancer 102, 638-42, 2002), microarray analysis demonstrated that the tongue cancers showed a distinct difference in gene expression ratios, for example of NQO1 gene, between the DA rat and WF rat.These results indicate that the DA rat and WF rat possibly show a distinct signature of differential gene expression in their tongue cancers of which histologic types are the same, I.e., squamous cell carcinoma.

在这里，我们报告使用cDNA微阵列来测量全球模式的基因表达在4-硝基喹啉1-氧化物（4 NQO）诱导的大鼠舌癌组织。基因表达的测量是两种大鼠品系（高度易感的Dark-Agglutinase（DA）大鼠和低易感的Wistar/Furth（WF）大鼠）的分子分化的基础（Kitano等，Jpn J Cancer Res 83，845-50，1992 ; Kitano等，Jpn J Cancer Res 87，1097-101，1996）。为了定量基因表达，将来自平行杂交到对照（Cy 3-标记）和4-硝基喹啉1-氧化物诱导的大鼠舌癌（Cy 5-标记）的两种大鼠品系的cDNA样品的微阵列的荧光重叠并分析。根据Cy 5/Cy 3信号强度的比率，将由四倍体杂交评价的表达因子确定为平均值。在本实验中，基因表达比率的3倍以上增加或减少被视为相关。在4 NQO诱导的DA大鼠舌癌（直径15 mm）中上调和下调的基因分别为337和220，在4 NQO诱导的WF大鼠舌癌（直径5 mm）中上调和下调的基因分别为182和81。关于先前描述的参与大鼠舌癌变易感性的QTL候选基因，（Tanuma等，Cancer Res 58，1660-4，1998 ; Tanuma等，Jpn J Cancer Res 92，610-6，2001 ; Tanuma等，Int J Cancer 102，638-42，2002），微阵列分析表明舌癌显示出基因表达比率的明显差异，例如NQO 1基因，这些结果表明，DA大鼠和WF大鼠在其组织学类型相同的舌癌中可能显示出差异基因表达的独特特征，即，鳞状细胞癌

项目成果

Tanuma J, Hiai H, Shisa H, Hirano M, Semba I, Nagaoka S, Kitano M.: "Carcinogenesis modifier loci in rat tongue are subject to frequent loss of heterozygosity"Int J Cancer. 102. 638-642 (2002)

Tanuma J、Hiai H、Shisa H、Hirano M、Semba I、Nagaoka S、Kitano M.：“大鼠舌头中的致癌修饰基因座经常发生杂合性丢失”Int J Cancer。

北野元生, 平野真人, 石原尚, 梅村恵理, 吉田愛知: "ラットにおけるハブ毒による組織傷害の特徴(筋肉壊死後の筋肉再生と出血のメカニズムについての考察)"鹿児島大学全学合同プロジェクト離島の豊かな発展のための学際的研究-離島学の構築(No.2)-. No.2. 97-102 (2002)

Motoo Kitano、Masato Hirano、Nao Ishihara、Eri Umemura、Aichi Yoshida：“HABU毒液引起大鼠组织损伤的特征（肌肉坏死后肌肉再生和出血的机制讨论）”鹿儿岛大学远程丰富性联合项目岛屿可持续发展的跨学科研究-偏远岛屿研究的建设（第2期）-第97-102号。

Hirano M, Tanuma J, Tsuneyoshi M, Kitano M, et al.: "Solitary fibrous tumor in the mental region"Pathol Intern. 51. 905-908 (2001)

Hirano M、Tanuma J、Tsuneyoshi M、Kitano M 等人：“精神区域孤立性纤维性肿瘤”Pathol Intern。

Kitano M.: "Host genes controlling the susceptibility and resistance to squamous cell carcinoma in a rat model"Pathol Intern. 50(5). 353-362 (2000)

Kitano M.：“宿主基因控制大鼠模型中鳞状细胞癌的易感性和抗性”Pathol Intern。

北野元生, 平野真人, 石原尚, 梅村恵理, 吉田愛知: "ラットにおけるハブ毒による組織障害の特徴(筋肉壊死後の筋肉再生と出血のメカニズムについての考察)"鹿児島大学全学合同プロジェクト離島の豊かな発展のための学際的研究-離島学の構築(No.2)-. (No.2). 97-102 (2002)

Motoo Kitano、Masato Hirano、Hisashi Ishihara、Eri Umemura、Aichi Yoshida：“哈布毒液引起大鼠组织损伤的特征（肌肉坏死后肌肉再生和出血的机制探讨）”鹿儿岛大学远程财富联合项目岛屿可持续发展的跨学科研究 - 偏远岛屿研究的建设（第 2 号）-（第 2002 年）。