A Role for ch1 in colorectal carcinoma

ch1 在结直肠癌中的作用

• 批准号: 09670246
• 负责人: TANAKA Kiyoko
• 金额: $ 1.86万
• 依托单位: Tokyo Metropolitan institute of Medical Science
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1997
• 资助国家: 日本
• 起止时间: 1997 至 1998
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09670246/
• 关键词: colorectal carcinama; screening; chromosome 1; cDNA library; northern blot; tumor suppressor gene; RACE; chromosome introduction; 1番染色体移入細胞; ノーザンブロット; cDNA-RDA

Development of colon carcinomas appears to be associated with inactivation of multiple tumor suppressor genes. Cytogenetic and DNA analyses of colon carcinoma have detected a high frequency of chromosome 1p deletion, which suggersts the presence of a tumor suppressor gene. So, we tried the isolation of tumor suppressor gene on chromosome 1 using nontumorigenic colon carcinoma cells containing normal chromosome 1p34-36 and tumorigenic revertantcells.A subtractive cDNA library specific to nontumorigenic colon carcinoma cells was constructed using oligo(dT)30-Latex. As a results of screening, we obtained a clone (G13) which expressed normal chromosome 1p34-36introduced cells and A9chl but not express parental COKFu and revertant cells. Northern bolt analysis revealed that G13 is highly expressed in normal mucosa but reduced in colon carcinomas. Next, we performed northern blot analysis on various human tissues, G13 transcripts were detected in colon, small intestine, ovary, testis, heart, and placenta and the gene evolutionarily conserved. Now, we try the full length gene by the RACE method.

结肠癌的发生似乎与多种肿瘤抑制基因的失活有关。细胞遗传学和DNA分析发现，结肠癌染色体1 p缺失的频率很高，这表明存在肿瘤抑制基因。因此，本研究利用含有正常染色体1 p34 -36的非致瘤性结肠癌细胞和致瘤性逆转录细胞，尝试分离1号染色体上的抑癌基因，并利用oligo（dT）30-Latex构建了非致瘤性结肠癌细胞特异性消减cDNA文库。筛选的结果是，我们获得了一个表达正常染色体1 p34 - 36导入细胞和A9 ch 1但不表达亲本COKFu和回复突变细胞的克隆（G13）。北方杂交分析显示，G13在正常粘膜中高表达，而在结肠癌中表达降低。接下来，我们对各种人体组织进行了北方印迹分析，在结肠、小肠、卵巢、睾丸、心脏和胎盘中检测到G13转录本，并且该基因在进化上是保守的。现在，我们尝试通过RACE方法获得全长基因。

项目成果

Miyaki,M & Tanaka,K: "Drastic genetic instability of tumors and normal tissues in Turcot syndrome" oncogene. 15. 2877-2881 (1997)

宫城，M

Miyaki, M., Konishi, M., Tanaka, K & Mori, T.: "Germline mutation of MSH6 as the cause of hereditary nonpolyposis colorectal cancer" Nature genetics. 17. 271-272 (1997)

宫城，M.，小西，M.，田中，K

Miyaki,M & Tanaka,K: "Germline mutation of MSH6 as the cause of herediatary nonpolyposis colorectal cancer" Nature genetics. 17. 271-272 (1997)

宫城，M

Miyaki, M., Nishio.J., Konishi, M., Yanishita, R., Tanaka, K & Utsunomiya, J.: "Drastic genetic instability of tumors and normal tissues in Turcot syndrome" oncogene. 15. 2877-2781 (1997)

Miyaki, M.、Nishio.J.、Konishi, M.、Yanishita, R.、Tanaka, K

Miyaki,M.: "Germline mutation of MSH6 as hte cause of hereditary nopolyposis colorectal cancer." Nature Genetics. 17. 271-272 (1997)

Miyaki,M.：“MSH6 种系突变是遗传性息肉病性结直肠癌的原因。”