STUDY OF TUM0R SUPPRESSOR GENE AND ANGIOGENESIS IN ORAL CAJNCER -Effect of the transfection of p53 and p16 tumor suppressor genes on angiogenesis-.

口腔癌肿瘤抑制基因和血管生成的研究-p53和p16肿瘤抑制基因转染对血管生成的影响-。

• 批准号: 12671937
• 负责人: KISHIMOTO Koji
• 金额: $ 2.11万
• 依托单位: OKAYAMA UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2001
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12671937/
• 关键词: oral squamous cell carcinoma; tumor suppressor gene p16 and p53; angiogenic factor; VEGF; PD-ECGF; VEGF-C; 癌抑制遺伝子p16; 遺伝子導入; 脱メチル化剤

I) Effect of tumor suppressor gene p53 and p16 on angiogenesisAs a result of SCC cell lines, HSC-4 was mutated R74 (CGA) to end codon (TGA) in exon 2 and SCC-4 was detected in the deletion of exon 2/3 splice acceptor site. They showed strong expression of VEGF.II) Expression of angiogenic factor and tumor suppressor gene, and their clinicopathological implications in oral squamous cell carcinomasWe investigated the expression of VEGF, PD-ECGF, VEGF-C, p53 and p16, and their clinicopathological implications in oral squamous cell carcinomas by immunohistochemistry. Intratumor microvessel density was evaluated with the number of positive microvessels for CD31 antibody. Results : VEGF-C expression correlated with lymph node metastasis (p < 0.01). According to stepwise logistic regression analysis, univarate analysis showed lymph node metastasis correlated with mode of invasion, VEGF-C expression and vessel invasion (p < 0.05). Moreover, multivariate analysis revealed that mode of invasion and VEGF-C expression were the exclusive indipendent factors influencing lymph node metastasis (p < 0.05). PD-ECGF correlated with, intratumor microvessel density (p < 0.05). VEGF, tumor differentiation, mode of invasion and lymph node metastasis were found to be significant in survival probability (p < 0.05), and VEGF and lymph node metastasis were independent prognostic factors in the Cox's multivariate proportional hazard model. Conclusions : It was suggested that the expression of VEGF, PD-ECGF, and VEGF-C in oral squamous cell carcinoma mainly correlated with prognosis, angiogenesis, lymph node metastasis respectively. However, tumor suppressor gene p53 and p16 did not correlate with metastasis and prognosis.

一、抑癌基因p53和p16对血管生成的影响SCC细胞株的结果显示，HSC-4在外显子2处发生了R74（CGA）突变为末端密码子（TGA），SCC-4在外显子2/3处存在剪接受体位点的缺失。二、血管生成因子和抑癌基因在口腔鳞癌中的表达及其临床病理意义采用免疫组化方法检测口腔鳞癌中VEGF、PD-ECGF、VEGF-C、p53和p16的表达及其临床病理意义。用CD 31抗体阳性微血管数评价肿瘤内微血管密度。结果：VEGF-C表达与淋巴结转移有关（P < 0.01）。逐步Logistic回归分析显示，单变量分析显示，淋巴结转移与浸润方式、VEGF-C表达及血管浸润有关（p < 0.05）。多因素分析显示，浸润方式和VEGF-C表达是影响淋巴结转移的唯一独立因素（p < 0.05）。PD-ECGF与肿瘤内微血管密度相关（p < 0.05）。VEGF、肿瘤分化程度、浸润方式和淋巴结转移对生存率有显著影响（p < 0.05），在考克斯多因素比例风险模型中VEGF和淋巴结转移是独立的预后因素。结论：提示VEGF、PD-ECGF、VEGF-C在口腔鳞癌中的表达分别与口腔鳞癌的预后、血管生成、淋巴结转移密切相关。而抑癌基因p53、p16与肿瘤转移及预后无关。