MODULATION OF GROWTH GENE-EXPRESSION BY SELECTIVE ALTERATION OF POLYAMINES IN HUMAN-COLON CARCINOMA-CELLS
MODULATION OF GROWTH GENE-EXPRESSION BY SELECTIVE ALTERATION OF POLYAMINES IN HUMAN-COLON CARCINOMA-CELLS
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DOI：
10.1016/0006-291x(89)91082-6
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发表时间：
1989-11-30
影响因子：
3.1
通讯作者：
CASERO, RA
中科院分区：
文献类型：
--
作者：
CELANO, P;BERCHTOLD, CM;CASERO, RA
多胺、腐胺、亚精胺和精胺的生物合成与许多生长相关基因的表达在时间上相关。我们以前的研究表明，2-二氟甲基鸟氨酸对人结肠癌细胞系科洛320的广义多胺耗竭与c-myc、c-fos和鸟氨酸脱羧酶（ODC）基因的转录降低有关。在目前的研究中，个别多胺的作用，进一步确定了使用的特异性抑制剂的亚精胺合酶，S-腺苷-1，8，diamino-3-thio-octane（ADATO），和精胺类似物，N1，N12双（乙基）精胺。我们的数据表明，亚精胺的耗竭导致c-myc mRNA稳定水平下降60-90%。相反，c-fos mRNA水平下降，只有当亚精胺和精胺都减少。此外，当DFMO降低所有多胺时，ODC水平增加，但不受ADDATO选择性降低细胞内亚精胺水平的影响。这些研究表明，个别多胺可能具有选择性的作用，在特定的生长相关基因的表达。
The biosynthesis of the polyamine, putrescine, spermidine and spermine, is temporally linked with expression of many growth related genes. Our previous studies have shown that generalized polyamine depletion of the human colon cancer cell line COLO 320 by 2-difluoromethylornithine is associated with decreased transcription of the c-myc, c-fos, and ornithine decarboxylase (ODC) genes. In the current study, the role of individual polyamines was further defined by the use of a specific inhibitor of spermidine synthase, S-adenosyl-1,8, diamino-3-thio-octane (AdoDATO), and a spermine analogue, N1,N12 bis(ethyl)spermine. Our data demonstrate that depletion of spermidine results in a 60-90% decrease in c-myc mRNA steady levels. In contrast, c-fos mRNA levels are decreased only when both spermidine and spermine are diminished. Furthermore, ODC levels are increased when all polyamines are decreased bu DFMO, but are unaffected by a selective reduction in intracellular spermidine levels by AdoDATO. These studies suggest that individual polyamines may have a selective role in the expression of specific growth related genes.