The functional analysis and clinical application of the metastasis-associated gene TI-241.

转移相关基因TI-241的功能分析及临床应用。

• 批准号: 10671159
• 负责人: ISHIGURO Tatsuaki
• 金额: $ 2.05万
• 依托单位: The University of TOKYO
• 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-10671159/
• 关键词: cancer metastasis; metastasis-associated gene; TI-241; ATF3; アンチセンスオリゴヌクレオチド; HT29

We performed differential screening between melanoma sublines of dirrerent metastatic potentials and isolated several genes that were differentially expressed between them. Most of these genes were already reported, but some were not. In those, TI227 showed no homology with formaly reported genes and differentally expressed in the sublines of colon cancer cells with different metastatic potential. This gene was expressed more in the highly experimentally metastatic subline of colon cancer cells. We analyzed its sequence and isolated its human counterpart TI227H. From the homology research between TI227 and TI227H, the most possible ORF was determined. We further isolated genomic DNA containing TI227 and analysed its 5' upstream sequence. TI227 was expected to be used in the diagnosis of metastatic potential and prognosis. Another gene TI241 showed homology with transcription factors of LRF1 and ATP3. Its transfection to the low metastatic subclone strengthened its metastatic potential and its expression in the metastatic foci was elevated. In the study using surgically excised specimens, its expression was expressed more in the cases with vascular invasions and its importance as a prognosis predictor was expected. Also from the study with the antisense oligonucleotides, TI241 was shown to relate cell adhesion and invasion and was thought to relate in vivo growth. From the exp6riments using nude mice, it surpressed subcutaneus growth and lengthened their survival period, which opened a possibility of its application to the gene therapy. Above results were already published or submitted to the English journals.

我们对具有不同转移潜力的黑色素瘤亚系进行了差异筛选，并分离出了它们之间差异表达的几个基因。这些基因中的大多数已经被报道，但有些还没有。其中，TI227与已报道的基因无同源性，在不同转移潜能的结肠癌细胞亚系中差异表达。该基因在结肠癌细胞的高转移性亚系中表达更多。我们分析了它的序列，并分离出它的人类对应物TI227H。通过对TI227和TI227H的同源性分析，确定了最可能的ORF。我们进一步分离了含有TI227的基因组DNA并分析了其5'上游序列。TI227有望用于转移潜能和预后的诊断。另一个基因TI241与转录因子LRF1和ATP 3同源。其转染低转移亚克隆增强了其转移潜能，并在转移灶中表达增加。在使用手术切除标本的研究中，其表达在血管浸润的病例中表达更多，并且预期其作为预后预测因子的重要性。同样从使用反义寡核苷酸的研究中，显示TI241与细胞粘附和侵袭相关，并且被认为与体内生长相关。从裸鼠实验来看，它抑制了皮下生长，延长了裸鼠的生存期，为它在基因治疗中的应用开辟了可能。以上结果已发表或提交英文期刊。

项目成果

Ishiguro T, et al.: "Enhanced metastasis of B16 melanoma cells by unexpected elevated expression of the metastatis-associated TI-241 (LRF-1-Jun-Fos-related) gene treated with antisense oligonucleotide"Clinical and Experimental Metastasis. 16. 179-83 (1998

Ishiguro T 等人：“用反义寡核苷酸处理的转移相关 TI-241（LRF-1-Jun-Fos 相关）基因的表达意外升高，从而增强了 B16 黑色素瘤细胞的转移”临床和实验转移。

T.Ishiguro et al: "Enhanced mecastasis of B16 meldnemd cells by unexpected elevored expression of the mefastasis-associated TI-241 gene treated with antisense oligonuclectide." Clinical & Experimental Metastasis.16(2). 179-83 (1998)

T.Ishiguro 等人：“用反义寡核苷酸处理后，与细胞转移相关的 TI-241 基因的表达出人意料地升高，从而增强了 B16 meldnemd 细胞的细胞转移。”

Ishiguro T. et al.: "Enhanced metastasis of B16 melanoma cells by unexpected elevated expression of the metastasis-associated TI241 (LRF-1, Jun-Fos-related) gene treated with antisense oligonucleotide."Clinical and experimental metastasis. 16(2). 179-183

Ishiguro T. 等人：“用反义寡核苷酸处理的转移相关 TI241（LRF-1、Jun-Fos 相关）基因的表达意外升高，从而增强了 B16 黑色素瘤细胞的转移。”临床和实验转移。

Hoshina K. et al.: "Three generations of hereditary chronic pancreatitis"Hepatogastroenterology. 46. 1192-1198 (1999)

Hoshina K.等：“三代遗传性慢性胰腺炎”肝胃肠病学。

Hoshina K, et al.: "Three generations of hereditary chronic pancreatitis"Hepatogastroenterology. 46. 1192-8 (1999)

Hoshina K，等：“三代遗传性慢性胰腺炎”肝胃肠病学。