Resarch of novel tumor metastasis-related genes for lung canncer

新型肺癌肿瘤转移相关基因的研究

• 批准号: 10671269
• 负责人: YASUDA Shin-ichi
• 金额: $ 2.18万
• 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: 1998
• 资助国家: 日本
• 起止时间: 1998 至 1999
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10671269/
• 关键词: human lung cancer; subtraction; tumor metastasis-related genes; ectopic transplantation; 肺癌; 骨軟部腫瘍; 癌浸潤・転移; 接着分子; 線溶系分子; 転移制御因子

Invasion of malignant cells from primary tumors and subsequent metastasis critically influence mortality among cancer patients, but the genetic and biological mechanisms involved are still poorly understood. Metastasis is a complex series of events in which some genes function as stimulatory factors and others inhibit the process ; presumably, an imbalance among several such genes induces metastasis.We have used a system that combines the subtractive suppression hybridization (SSH) with high throughput differential screening for search of metastasis related genes. The cell lines HAL were establishment from human lung adenocarcinoma in our laboratory, the sublines HAL-8 was metastatic cell line to inject intramuscularly in nude mice while HAL-24 cells do not. SSH technique was used to subtract the RNA distinguishing metastatic HAL-8 and non-metastatic HAL-24 cells.The cDNA fragments of subtract were trasfected to the compitents cells and recovered from the transcripts in compitents cells were analyzed by sequences. Comparison of the sequences obtained by PCR with genome databases provided that the isolated DNA of several represented genes and novel genes for weakly linked to trophoblast, the latter is analyzing cDNA library of HAL cells.

原发肿瘤的恶性细胞侵袭和随后的转移严重影响癌症患者的死亡率，但其涉及的遗传和生物学机制仍然知之甚少。转移是一系列复杂的事件，其中一些基因起刺激因子的作用，另一些基因则抑制这一过程；推测这些基因之间的失衡会导致转移。我们使用了一种结合消减抑制杂交(SSH)和高通量差异筛选的系统来寻找与转移相关的基因。本实验室建立了人肺腺癌HAL细胞系，HAL-8亚系是裸鼠肌肉注射的转移性细胞株，而HAL-24细胞不是。采用SSH技术提取HAL-8细胞和未转移HAL-24细胞的RNA，并将该消减产物的cdna片段导入细胞并从转录产物中回收，进行序列分析。通过与基因组数据库的序列比较发现，分离的几个有代表性的基因和与滋养层细胞弱连锁的新基因，后者正在分析HAL细胞的cDNA文库。

项目成果

Hayashi M, Yasuda S: "Establishment and characterization of a new human synovial sarcoma cell line H-SS-HSY which product hyaluronan"Dokkyo J Med.Science. 27. 49-56 (2000)

Hayashi M、Yasuda S：“产生透明质酸的新人类滑膜肉瘤细胞系 H-SS-HSY 的建立和表征”Dokkyo J Med.Science。

M.Hayashi, S.Yasuda, et al.: "Establishment and characterization of a new human synovialsarcoma cell line H-SS-HSY which produce hyaluronan"Dokkyo J Med.Science. 27. 49-56 (2000)

M.Hayashi、S.Yasuda 等人：“产生透明质酸的新型人类滑膜肉瘤细胞系 H-SS-HSY 的建立和表征”Dokkyo J Med.Science。