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丁酸钠对人结肠肿瘤细胞系HT29中视网膜母细胞瘤(RB1)和P53基因表达及视网膜母细胞瘤蛋白磷酸化的影响

Effect of sodium butyrate on the expression of retinoblastoma (RB1) and P53 gene and phosphorylation of retinoblastoma protein in human colon tumor cell line HT29.

作者信息

Gope R, Gope M L

机构信息

Creighton University School of Medicine, Creighton Cancer Center, Omaha, NE 68178.

出版信息

Cell Mol Biol (Noisy-le-grand). 1993 Sep;39(6):589-97.

PMID:8220069
Abstract

Sodium butyrate is known to induce morphological and biochemical changes associated with cell differentiation in some colon tumor cell lines including HT29. In our present study we observed that sodium butyrate treatment caused a decrease in the level of expression of RB1 gene on day seven of butyrate treatment but a gradual six to sevenfold decrease in the level of expression of p53 gene. Western blot analysis revealed a decrease in the level of the phosphorylated form of Rb protein (pRb) and an increase in the level of underphosphorylated pRb as compared to the control cells. These changes in the phosphorylation level were observed from day three of sodium butyrate treatment. In addition, the flat foci forming large differentiated cells also began to appear after 3 days of sodium butyrate treatment. In this study, we are able to show that, besides induction of differentiation, sodium butyrate treatment can also cause a reversal in the phosphorylation status of the pRb in colon tumor cell line HT29. These results suggest that the phosphorylation level of pRb could be associated with the cell differentiation process in human colonic epithelium and as a consequence in its neoplastic development.

摘要

已知丁酸钠可诱导包括HT29在内的一些结肠肿瘤细胞系发生与细胞分化相关的形态和生化变化。在我们目前的研究中,我们观察到在丁酸钠处理的第7天,丁酸钠处理导致RB1基因表达水平下降,但p53基因表达水平逐渐下降6至7倍。蛋白质印迹分析显示,与对照细胞相比,Rb蛋白(pRb)的磷酸化形式水平下降,而低磷酸化pRb水平增加。从丁酸钠处理的第3天开始观察到磷酸化水平的这些变化。此外,在丁酸钠处理3天后,形成大的分化细胞的扁平病灶也开始出现。在这项研究中,我们能够表明,除了诱导分化外,丁酸钠处理还可导致结肠肿瘤细胞系HT29中pRb的磷酸化状态发生逆转。这些结果表明,pRb的磷酸化水平可能与人类结肠上皮细胞的分化过程相关,并因此与其肿瘤发生发展相关。

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