Molecular Oncological Analysis of Human Kidney Tumors

人肾肿瘤的分子肿瘤学分析

• 批准号: 63570747
• 负责人: FUJITA Jun
• 金额: $ 1.34万
• 依托单位: Osaka University Medical School
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1988
• 资助国家: 日本
• 起止时间: 1988 至 1989
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-63570747/
• 关键词: Oncogene; Kidney tumor; Chimeric mouse; Anti-oncogene; carcinogenesis; Ras oncogene; 多段階発癌; 点突然変異; DNAトランスフェクション; 染色体欠失; 体細胞変異

Two H-ras oncogenes were detected bY NIH/3T3 transfection assay out of 16 primary kidney tumors, 15 renal cell carcinomas (RCC), and one transitional cell carcinoma in 16 patients. Analysis of ras M_r 21,000 protein suggested single point mutations within codon 12 and 61 in each case. The restriction endonuclease analysis of H-ras gene at codon 12 confirmed this in one of them, and the remaining 15 tumors did not have a mutation at this site. DNAs from the noncancerous portions of the kidney with codon 12 mutated tumor, but not leukocytes from the same patient, showed an abnormal resistance to the endonucleases MspI and HpaII, suggesting a presence of codon 12 mutated H-ras gene in the noncancerous cells. No amplification of ras genes was detected in the 16 tumors analyzed. In one of eight tumors from patients heterozygous for H-ras related BamHI restriction fragments, one allele was lost in the tumor but not in the noncancerous portion of the same kidney. Although cytogenetic studies have previously suggested nonrandom involvement of c-raf-1 gene in RCC, no abnormality in the size nor amount of raf transcript was detected in the 15 RCCs. Our results thus indicated that the genetic lesions affecting ras genes do occur in human RCC, and probably serve as one of multisteps in the carcinogenic process.

采用NIH/3T3转染法，从16例原发性肾肿瘤、15例肾细胞癌（RCC）和16例移行细胞癌中检测到2个H-ras癌基因。对ras m_r21000蛋白的分析表明，每个病例的密码子12和61内存在单点突变。其中1例在密码子12处的H-ras基因的限制性内切酶分析证实了这一点，其余15例肿瘤在该位点未发生突变。来自具有密码子12突变肿瘤的肾脏非癌部分的dna，而来自同一患者的白细胞的dna，对内切酶MspI和HpaII表现出异常的抗性，这表明非癌细胞中存在密码子12突变的H-ras基因。在所分析的16个肿瘤中未检测到ras基因扩增。在8个与H-ras相关的BamHI限制性片段杂合的肿瘤患者中，有一个在肿瘤中丢失了一个等位基因，但在同一肾脏的非癌部分却没有丢失。尽管先前的细胞遗传学研究表明c-raf-1基因在RCC中非随机参与，但在15例RCC中未检测到raf转录物的大小和数量异常。因此，我们的研究结果表明，影响ras基因的遗传病变确实发生在人类RCC中，并且可能是致癌过程的多个步骤之一。

项目成果

Nakayama,H.: "Kidney proximal tuble cells originate from approximately four progenitor cells and make distinct patches in mouse aggregation chimeras" Develop.Growth Differ.31. 79-83 (1989)

Nakayama, H.：“肾近端小管细胞起源于大约四个祖细胞，并在小鼠聚集嵌合体中形成不同的斑块”Develop.Growth Differ.31。

Sugimoto,K.: "Prosence of an activity indispensable for the granulocyte/macrophage colonyーstimulating activity of interleukinー3 in BSA." Leukemia Res.

Sugimoto, K.：“BSA 中白细胞介素 3 的粒细胞/巨噬细胞集落刺激活性所必需的活性的存在。”

Fujita,J.: "Detection of ras oncogenes by analysis of p21 proteins in human tumor cell lines" Urol.Res.16. 415-418 (1988)

Fujita,J.：“通过分析人肿瘤细胞系中的 p21 蛋白检测 ras 癌基因”Urol.Res.16。

Nakayama,H.: "Kidney proximal tubule cells originate from approximately four progenitor cells and make distinct patches in mouse aggregation chimeras" Develop.Growth Differ.31. 79-83 (1989)

Nakayama, H.：“肾近端小管细胞起源于大约四个祖细胞，并在小鼠聚集嵌合体中形成不同的斑块”Develop.Growth Differ.31。

Nakayama, H., Kuroda, H., Fujita, J., Ru, X.-M. and Kitamura, Y.: "Kidney proximal tubule cells originate from approximately four progenitor cells and make distinct patches in mouse aggregation chimeras." Develop. Growth Differ., 31, 79-83, 1989.

中山，H.，黑田，H.，藤田，J.，Ru，X.-M。