New metastasis regulated genes from human lung carcinoma to functional analysis and application for therapy

人肺癌新转移调控基因的功能分析和治疗应用

• 批准号: 13671404
• 负责人: YASUDA Shin-ichi
• 金额: $ 2.3万
• 依托单位: Dokkyo University School of Medicine
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13671404/
• 关键词: lung carcinoma; ectropic inoculation; tumor metastasis regulated gene; 異所性転移細胞; 転移制御関連遺伝子; 転移制御遺伝子; サブトラクション法

A metastasis from primary tumor is concluded through many processes. It is the important problem, which relates to the patient's prognosis closely and to make this analysis of the therapy for the cancer. We established the lung cancer cell line, which it only metastasis to the lung. Subtraction was carried out between metastasis and non-metastasis cells. We analyzed four genes, which related to the metastasis. Laminin receptor (LR) gene is specific receptor toward cell adhesion protein to laminins. It was proved that there was a loss of exson in a part of the gene that a code does a 67kDa molecule as an analysis. And, PAF-AH is acetylhydlase of the activated factor of the phospholipids (PAF), which produced of the platelets, which relates to the tumor metastasis. It is involved in the movement of the nerve cell, but the cancer metastasis isn't clear. Participation is suggested to the metastasis control due to inactivation of PAF due to the expression of this PAF-AH gene with the non-metastasis line. Furthermore, RACE method was enforced, and it got the gene of the extension to analyze two unknown genetic fragments. These genes are related to the melanoma, one of others existed in 14 chromosome, which relates to the uterine cervix carcinoma and the intestine mucous membrane protein, and agreement were entry of Gene bank with it recently The genes are presumed probably to be the molecule, which relates to the natural metastasis mechanism but couldn't get the functional events for metastasis.

原发肿瘤的转移是通过许多过程完成的。这是与患者预后密切相关的重要问题，对肿瘤的治疗进行分析。我们建立了肺癌细胞株，它只转移到肺。在转移和非转移细胞之间进行减法。我们分析了四个与肿瘤转移相关的基因。层粘连蛋白受体（LR）基因是层粘连蛋白对细胞粘附蛋白的特异性受体。经分析证明，该基因编码一个67 kDa分子的部分外显子缺失。而PAF-AH是血小板产生的磷脂活化因子（PAF）的乙酰水解酶，与肿瘤转移有关。它与神经细胞的运动有关，但与肿瘤转移的关系尚不清楚。由于该PAF-AH基因在非转移细胞系中的表达导致PAF失活，因此提示参与转移控制。同时，采用RACE方法，对两个未知的基因片段进行了分析，得到了该延伸段的基因。这些基因与黑色素瘤有关，其中一个基因存在于14号染色体上，与宫颈癌和肠粘膜蛋白有关，最近已被基因库收录，推测这些基因可能是与肿瘤自然转移机制有关，但不能获得转移功能事件的分子。