Suppression of tumor phenotypes of human colon carcinoma cells by introduction of normal chromosomes

通过引入正常染色体抑制人结肠癌细胞的肿瘤表型

• 批准号: 03670186
• 负责人: TANAKA Kiyoko
• 金额: $ 0.38万
• 依托单位: The Tokyo Metropolitan Institute of Medical Science
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1991
• 资助国家: 日本
• 起止时间: 1991 至 1992
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-03670186/
• 关键词: Human colon cancer; chromosome introduction; Tumor suppressor gene; 微小核融合法; 癌形質抑制; 大腸癌; 染色体移入

Development of colon carcinomas can be associated with allelic deletions on several chromosomes, including 5q and 17p. The APC gene on 5q and the p53 gene on 17q have been identified as potential tumor suppressor genes, whose suppression contributes to colon carcinogenesis. To investigate the role of genes in these deleted regions, we have introduced different normal human chromosomes into a colon carcinoma cells through microcell hybridization. The introduction of a normal chromosome 17 causes a decrease in the malignancy of colon carcinoma cells suppressing certain malignant phenotypes, such as morphology, growth in soft agar, although not all tumor phenotypes are suppressed. The hybrid cells with chromosome 17 were tumorigenic, but the tumor growth rate of these clones were consistently slower than that of parental colon carcinoma cells. Furthermore, the introduction of normal chromosome 5 into hybrid cells with chromosome 17 caused suppression of the growth of carcinoma cells. Introduction of different normal chromosomes into colon carcinoma cells brought a decrease in the malignancy.

结肠癌的发展可能与包括5q和17p在内的几条染色体上的等位基因缺失有关。5q上的APC基因和17q上的p53基因已被确定为潜在的肿瘤抑制基因，其抑制有助于结肠癌的发生。为了研究基因在这些缺失区域的作用，我们通过微细胞杂交将不同的正常人类染色体引入结肠癌细胞。引入正常的17号染色体导致结肠癌细胞的恶性减少，抑制某些恶性表型，如软琼脂中的形态和生长，尽管并非所有肿瘤表型都受到抑制。具有17号染色体的杂交细胞具有致瘤性，但这些克隆的肿瘤生长速度始终低于亲本结肠癌细胞。此外，将正常的5号染色体引入具有17号染色体的杂交细胞中，可以抑制癌细胞的生长。将不同的正常染色体引入结肠癌细胞后，恶性肿瘤的发生率降低。

项目成果

R.YANOSHITA,K.YANAKA et al.: "Genetic changes in both alleles of p53gene involved in the conversion of colorectal adenomas into early carinomas." Cancer Res.52. 3965-3971 (1992)

R.YANOSHITA、K.YANAKA 等人：“p53 基因的两个等位基因的遗传变化参与结直肠腺瘤向早期癌的转化。”

田中 貴代子他: "染色体移入により癌形質の抑制" 実験医学. 9. 59-62 (1991)

Kiyoko Tanaka 等人：“通过染色体转移抑制癌性特征”实验医学 9. 59-62 (1991)。

K.Tanaka et al: "Suppression of tumorigenicity in human colon carcinoma cells by introduction of normal chromosome 1p36 region" Onocogene. (1993)

K.Tanaka 等人：“通过引入正常染色体 1p36 区域抑制人结肠癌细胞的致瘤性”Onocogene。

宮木 美知子 田中 貴代子 他: "多段階発癌過程におけるp53遺伝子異常の意義" 実験医学. 10. 964-968 (1992)

Michiko Miyagi、Kiyoko Tanaka 等：“p53 基因异常在多步致癌过程中的意义”实验医学。10. 964-968 (1992)

K.TANAKA et al.: "Suppression of tumorigenicety in human colon carcinoma cells by introduction of normal chromosome 1p36 region." Onocogene.(1993)

K.TANAKA 等人：“通过引入正常染色体 1p36 区域抑制人结肠癌细胞的致瘤性。”