Development of specific vector containing FN-1 fused protein and SCCA promoter for esophageal cancer

食管癌FN-1融合蛋白和SCCA启动子特异性载体的研制

• 批准号: 14370370
• 负责人: OKUSHIBA Shunichi
• 金额: $ 9.15万
• 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: 2002
• 资助国家: 日本
• 起止时间: 2002 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14370370/
• 关键词: esophageal squamous cell carcinoma; gene therapy; RCAS1; caveolin-1; adenoviralvector; SCCA2 promotein; SCCAプロモーター; 非ウイルスベクター; 遺伝子解析; caveolin-1

We screened several gene expressions in esophageal squamous cell carcinoma (ESCC) for the purpose of finding of cancer specific gene expression and development of therapeutic gene. Then we found that RCAS1 and caveolin-1 are potentially useful for the target of esophageal cancer. Subsequently, we constructed a shuttle vector to make adenoviral vectors in which SCCA2 promoter was introduced. An adenoviral vector which expresses proapoptotic gene KLAKLA2 driven by SCCA2 promoter was reconstructed. Ad-SCCAp-KLAKLAK induced apoptosis in SCCA2 producing cell lines LK2 and LC1, but not A549 or ABC-1 that did not produce SCCA2. Effects of gene therapy using Ad-SCCAp-KLAKLAK were observed in vivo SCCA2 producing tumors implanted on the hack of nude mice were successfully suppressed by Ad-SCCAp-KLAKLAK.

为了寻找食管鳞状细胞癌（ESCC）的特异性基因表达，开发治疗基因，我们对食管鳞状细胞癌（ESCC）中的几种基因表达进行了筛选。我们发现RCAS 1和caveolin-1可能是食管癌治疗的靶点。随后，我们构建了一个穿梭载体，使腺病毒载体中引入SCCA 2启动子。构建了由SCCA 2启动子驱动的表达促凋亡基因KLAKLA 2的腺病毒载体。Ad-SCCAp-KLAKLAK在产生SCCA 2的细胞系LK 2和LC 1中诱导凋亡，但在不产生SCCA 2的A549或ABC-1中不诱导凋亡。用Ad-SCCA_p-KLAKLAK在裸鼠皮下移植瘤中观察了Ad-SCCA_p-KLAKLAK的基因治疗效果。

项目成果

Nakakubo Y: "The prognostic significance of RCAS1 expression in squamous cell carcinoma of the oesophagus"Cancer Letters. 177. 101-105 (2002)

Nakakubo Y：“食管鳞状细胞癌中 RCAS1 表达的预后意义”Cancer Letters。

Takahashi Y: "Expression profiles of 39 HOX genes in normal human adult organs and anaplastic thyroid cancer cell lines by quantitative real-time RT-PCR system"Experimental Cell Res. 293. 144-153 (2004)

Takahashi Y：“通过定量实时 RT-PCR 系统检测正常成人器官和未分化甲状腺癌细胞系中 39 个 HOX 基因的表达谱”实验细胞研究。

Cho Y: "CD4+ and CD8+ T Cells Cooperate to Improve Prognosis of Patients with Esophageal Squamous Cell Carcinoma."Cancer Res. 63. 1555-1559 (2003)

Cho Y：“CD4 和 CD8 T 细胞协同改善食管鳞状细胞癌患者的预后。”癌症研究。

Hideaki Hashida: "Fusion of Tat protein transduction domain to poly-lysine as a new DNA delivery tool."British Journal of Cancer. 90. 1252-1258 (2004)

Hideaki Hashida：“Tat 蛋白转导结构域与聚赖氨酸的融合作为新的 DNA 传递工具。”英国癌症杂志。

Hashida H: "Fusion of HIV-1 Tat protein transduction domain to poly-lysine as a new DNA delivery tool"Br J Cancer. 90. 1252-1258 (2004)

Hashida H：“HIV-1 Tat 蛋白转导结构域与聚赖氨酸的融合作为新的 DNA 传递工具”Br J Cancer。