多梳蛋白家族蛋白Bmi1是RAF驱动的非小细胞肺癌生长所必需的。
Polycomb group protein Bmi1 is required for growth of RAF driven non-small-cell lung cancer.
作者信息
Becker Matthias, Korn Christian, Sienerth Arnold R, Voswinckel Robert, Luetkenhaus Katharina, Ceteci Fatih, Rapp Ulf R
机构信息
Bayerisches Krebsforschungszentrum, University of Wuerzburg, Wuerzburg, Germany.
出版信息
PLoS One. 2009;4(1):e4230. doi: 10.1371/journal.pone.0004230. Epub 2009 Jan 19.
BACKGROUND
We have previously described a RAF oncogene driven transgenic mouse model for non small cell lung cancer (NSCLC). Here we examine whether tumor initiation and growth requires the stem cell self-renewal factor Bmi1.
PRINCIPAL FINDINGS
In order to evaluate Bmi1 function in NSCLC two founder lines that differ in incidence and latency of tumor formation were compared. Ablation of Bmi1 expression in both lines had a dramatically decreased tumor growth. As the line with shorter latency matched the life span of Bmi1 knock out mice, these mice were chosen for further study. The absence of Bmi1 did not decrease the number of tumor initiation in these mice as only the size and not the number of tumors decreased. Reduction in tumor growth resulted from an increase in cell death and decrease in cell cycle progression that corresponded with up-regulation of the p16(INK4a) and p19(ARF).
SIGNIFICANCE
The data identifies Bmi1 as an important factor for expansion but not initiation of RAF driven NSCLC.
背景
我们之前描述过一种由RAF癌基因驱动的非小细胞肺癌（NSCLC）转基因小鼠模型。在此，我们研究肿瘤的起始和生长是否需要干细胞自我更新因子Bmi1。
主要发现
为了评估Bmi1在NSCLC中的功能，我们比较了两个在肿瘤形成的发生率和潜伏期方面存在差异的奠基鼠系。在这两个鼠系中敲除Bmi1表达均使肿瘤生长显著减缓。由于潜伏期较短的鼠系与Bmi1基因敲除小鼠的寿命相匹配，因此选择这些小鼠进行进一步研究。在这些小鼠中，Bmi1的缺失并未减少肿瘤起始的数量，只是肿瘤的大小而非数量减小了。肿瘤生长减缓是由于细胞死亡增加以及细胞周期进程减慢，这与p16（INK4a）和p19（ARF）的上调相对应。
意义
这些数据表明Bmi1是RAF驱动的NSCLC扩增而非起始的重要因素。
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