Sodium butyrate suppresses the transforming activity of an activated N-ras oncogene in human colon carcinoma cells.
Sodium butyrate suppresses the transforming activity of an activated N-ras oncogene in human colon carcinoma cells.
复制标题
丁酸钠抑制人结肠癌细胞中激活的 N-ras 癌基因的转化活性。
DOI：
10.1016/0014-4827(89)90359-5
复制
发表时间：
1989
影响因子：
3.7
通讯作者：
Niles,RM
中科院分区：
文献类型：
--
作者：
Stoddart,JH;Lane,MA;Niles,RM
在 NIH-3T3 转染测定中测试了来自新建立的未分化人结肠癌细胞系 (MIP-101) 的 DNA 的转化活性。转染子 DNA 的 Southern 印迹分析揭示了人类 N-rasonco 基因的存在。用成熟剂丁酸钠处理 MIP-101 细胞会诱导更正常的表型，包括生长速率降低、锚定年龄独立生长的消除以及致瘤性降低（R. Niles、S. Wilhelm、P. Thomas 和 N. Zamcheck (1988)J. Cancer Invest.6, 39）。在此，我们报告丁酸盐处理的 MIP-101 细胞的 DNA 转化效率显着降低。通过显示丁酸盐处理和对照 MIP 细胞的 DNA 中胸苷激酶基因的摄取和表达相似，消除了作为这些发现的解释的总 DNA 摄取的非特异性减少。丁酸盐处理对 MIP-101 细胞中人 N-rasgene 的整体结构、甲基化和表达水平没有可检测到的影响。评估携带人N-rasgene的NIH-3T3转化体在丁酸钠处理后的表型回复和DNA转化能力。尽管丁酸盐抑制了与 MIP-101 细胞类似的几种转化特性，但来自对照和处理培养物的 DNA 具有相同水平的转化活性。结果表明，MIP 细胞的环境可能含有 NIH-3T3 转化体中不存在的其他元素，需要观察丁酸盐对转化活性降低的影响。
The transforming activity of DNA from a newly established undifferentiated human colon carcinoma cell line (MIP-101) was tested in the NIH-3T3 transfection assay. Southern blot analysis of the transfectant DNA revealed the presence of a human N-rasoncogene. Treatment of MIP-101 cells with the maturational agent sodium butyrate induced a more normal phenotype, including diminished growth rate, elimination of anchor-age independent growth, and decreased tumorigenicity (R. Niles, S. Wilhelm, P. Thomas, and N. Zamcheck (1988)J. Cancer Invest.6, 39). Here we report that there is a significant reduction in the transforming efficiency of the DNA from butyrate-treated MIP-101 cells. A nonspecific reduction in total DNA uptake as an explanation for these findings was eliminated by showing that there was similar uptake and expression of the thymidine kinase gene from the DNA of butyrate-treated and control MIP cells. Butyrate treatment had no detectable effect on the overall structure, methylation, and level of expression of the human N-rasgene from MIP-101 cells. An NIH-3T3 transformant carrying the human N-rasgene was evaluated for phenotypic reversion and DNA transforming ability after treatment with sodium butyrate. Although butyrate suppressed several transformed properties similar to MIP-101 cells, DNA from control and treated cultures had an identical level of transforming activity. The results suggest that the environment of the MIP cells may contain additional elements not present in the NIH-3T3 transformants which are required to observe the effect of butyrate on reduction of transforming activity.