KRAS-mediated up-regulation of RRM2 expression is essential for the proliferation of colorectal cancer cell lines.
KRAS-mediated up-regulation of RRM2 expression is essential for the proliferation of colorectal cancer cell lines.
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发表时间：
2011-07
影响因子：
2
通讯作者：
Y. Yoshida;T. Tsunoda;Keiko Doi;Yoko Tanaka;T. Fujimoto;Takashi Machida;Takeharu Ota;Midori Koyanagi-Midori-K
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作者：
Y. Yoshida;T. Tsunoda;Keiko Doi;Yoko Tanaka;T. Fujimoto;Takashi Machida;Takeharu Ota;Midori Koyanagi-Midori-K
我们之前通过微阵列分析研究了结直肠癌细胞系的mRNA表达，发现在血清饥饿条件下，几个基因被致癌KRAS显著上调。在这些基因中，我们重点研究了核糖核苷酸还原酶M2 (RRM2)，据报道它与DNA合成有关。材料和方法用转染慢病毒rrm2 - shrna的HCT116细胞进行细胞增殖和集落形成实验。结果血清饥饿条件下，HCT116细胞中RRM2蛋白的表达水平高于HKe3细胞（HCT116细胞中致癌KRAS被破坏），HKe3细胞中KRAS的重新表达诱导了RRM2的表达。降低RRM2蛋白的表达，使血清缺失条件下的细胞增殖和非锚定生长受到损害。结论RRM2是一种新的治疗靶点，因此强调了RRM2抑制剂在结直肠癌致癌KRAS中的潜在效用。
BACKGROUND We previously investigated the mRNA expression of colorectal cancer cell lines via a microarray analysis and found several genes that were significantly up-regulated by oncogenic KRAS under serum-starved conditions. Of these genes, we focused on ribonucleotide reductase M2 (RRM2), which was reported to be associated with DNA synthesis. MATERIALS AND METHODS Cell proliferation and colony formation assays were performed using HCT116 cells transfected with lentiviral RRM2-shRNAs. RESULTS Under serum-starved conditions, the expression level of RRM2 protein increased in HCT116 cells compared to HKe3 cells (HCT116 cells with a disruption in oncogenic KRAS), and the re-expression of KRAS in HKe3 cells induced the expression of RRM2. Both the cell proliferation under serum-depleted conditions and the anchorage-independent growth were impaired by the reduction of RRM2 protein expression. CONCLUSION RRM2 represents a novel therapeutic target, thus highlighting the potential utility of RRM2 inhibitors in colorectal cancer with oncogenic KRAS.