REGULATION OF C-MYC EXPRESSION BY SODIUM-BUTYRATE IN THE COLON-CARCINOMA CELL-LINE CACO-2

被引:66
作者
SOULEIMANI, A [1 ]
ASSELIN, C [1 ]
机构
[1] UNIV SHERBROOKE, FAC MED, DEPT ANAT & BIOL CELLULAIRE, RECH BIOL DEV GRP, SHERBROOKE J1H 5N4, QUEBEC, CANADA
来源
FEBS LETTERS | 1993年 / 326卷 / 1-3期
基金
英国医学研究理事会;
关键词
C-MYC; BUTYRATE; CACO-2; CROSS-LINK; MESSENGER RNA STABILITY; RUN-ON;
D O I
10.1016/0014-5793(93)81758-R
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The human colon carcinoma cell line Caco-2 spontaneously undergoes enterocytic differentiation in culture. We used sodium butyrate to modify differentiation and growth properties of this cell line and considered c-myc expression as a potential target. Degradation of normal c-myc mRNAs with a half-life of 20 min is not coupled to translation in this cell line, as determined by cycloheximide treatment. We show that butyrate reduces c-myc mRNA levels after a 30 min delay. Butyrate does not affect c-myc expression at the level of transcriptional initiation or elongation, as determined by run-on analysis, but at a post-transcriptional level. Cycloheximide blocks butyrate-dependent reduction of c-myc mRNA levels. Cross-linking experiments show that a 34 kDa protein binds specifically to the c-myc AU-rich instability determinant found in the 3'-untranslated region (ARE). Binding of this protein to the ARE is not modulated by butyrate or cycloheximide. These experiments suggest that butyrate induces a factor involved in c-myc mRNA degradation that differs from the known ARE-associated proteins. Post-transcriptional modification of gene expression could be one of the major targets for this anti-proliferative agent.
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页码:45 / 50
页数:6
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