Guo Q M, Malek R L, Kim S, Chiao C, He M, Ruffy M, Sanka K, Lee N H, Dang C V, Liu E T
Molecular Signaling and Oncogenesis Section, Department of Cancer and Cell Biology, Medicine Branch, Division of Clinical Science, National Cancer Institute, Bethesda, Maryland 20892, USA.
Cancer Res. 2000 Nov 1;60(21):5922-8.
c-Myc functions through direct activation or repression of transcription. Using cDNA microarray analysis, we have identified c-Myc-responsive genes by comparing gene expression profiles between c-myc null and c-myc wild-type rat fibroblast cells and between c-myc null and c-myc null cells reconstituted with c-myc. From a panel of 4400 cDNA elements, we found 198 genes responsive to c-myc when comparing wild-type or reconstituted cells with the null cells. The plurality of the named c-Myc-responsive genes that were up-regulated, including 30 ribosomal protein genes, are involved in macromolecular synthesis and metabolism, suggesting a major role of c-Myc in the regulation of protein synthetic and metabolic pathways. When ectopically overexpressed, c-Myc induced a different and smaller set of c-Myc-responsive genes as compared with the physiologically expressed c-Myc condition. Thus, these results from expression profiling suggest a new primary function for c-Myc and raise the possibility that the physiological and transforming functions of c-myc may be separable.
c-Myc 通过直接激活或抑制转录发挥作用。利用 cDNA 微阵列分析，我们通过比较 c-myc 基因敲除的大鼠成纤维细胞与 c-myc 野生型大鼠成纤维细胞之间以及 c-myc 基因敲除细胞与用 c-myc 重构的 c-myc 基因敲除细胞之间的基因表达谱，鉴定出了 c-Myc 反应性基因。在一组 4400 个 cDNA 元件中，当将野生型或重构细胞与基因敲除细胞进行比较时，我们发现了 198 个对 c-Myc 有反应的基因。许多上调的被命名为 c-Myc 反应性基因，包括 30 个核糖体蛋白基因，都参与大分子合成和代谢，这表明 c-Myc 在蛋白质合成和代谢途径的调节中起主要作用。与生理表达的 c-Myc 条件相比，当 c-Myc 异位过表达时，它诱导的 c-Myc 反应性基因集不同且数量较少。因此，这些表达谱分析结果表明 c-Myc 具有一种新的主要功能，并增加了 c-myc 的生理功能和转化功能可能是可分离的可能性。
