Lensch Ramona, Götz Claudia, Andres Christine, Bex Axel, Lehmann Jan, Zwergel Thomas, Unteregger Gerhard, Kamradt Jörn, Stoeckle Michael, Wullich Bernd
Department of Urology and Pediatric Urology, University of the Saarland, D-66421 Homburg/Saar, Germany.
Int J Oncol. 2002 Oct;21(4):695-706.
We recently reported on a prostate cancer progression model which was based on repeated orthotopic implantation of human prostate cancer cell lines into athymic nude mice leading to an increase of tumor cell aggressiveness. To assess progression-associated clonal evolution of genotypic changes, we now performed comparative cytogenetic characterization of the original cell lines DU145 and PC3 with derived sublines DU145MN1 and PC3-N. Cell line PC3-125-1L, isolated from a lung metastasis after subcutaneous inoculation of PC3 into nude mice, was included in the study. Whole-genome analysis was performed using spectral karyotyping and comparative genomic hybridization. Fluorescence in situ hybridization was used to assess amplification of selected genes, which are supposed to play a role in prostate cancer progression. Differences in the genetic constitution between parental cell lines and sublines involved gains of genetic material at 2q, 5q, 12p/q, and 18p as well as losses at 6p, 7q, 17p, 18q, and 22q. Loss of 17p in DU145MN1 and high-level amplification of MYC in PC3-125-1L resulted in loss of p53 expression and upregulation of Myc expression, respectively, as was assessed by Western blotting. Thus, the nude mice model is very useful to follow clonal evolution of genetic changes during increase of prostate cancer aggressiveness and possibly to clone genes associated with the progression of prostate cancer.
我们最近报道了一种前列腺癌进展模型，该模型基于将人前列腺癌细胞系反复原位植入无胸腺裸鼠体内，从而导致肿瘤细胞侵袭性增加。为了评估与进展相关的基因型变化的克隆进化，我们现在对原始细胞系DU145和PC3以及衍生亚系DU145MN1和PC3-N进行了比较细胞遗传学特征分析。从将PC3皮下接种到裸鼠后分离出的肺转移灶中获得的细胞系PC3-125-1L也纳入了研究。使用光谱核型分析和比较基因组杂交进行全基因组分析。荧光原位杂交用于评估选定基因的扩增情况，这些基因被认为在前列腺癌进展中起作用。亲代细胞系和亚系之间的遗传构成差异包括2q、5q、12p/q和18p处遗传物质的增加以及6p、7q、17p、18q和22q处的缺失。通过蛋白质印迹法评估发现，DU145MN1中17p的缺失和PC3-125-1L中MYC的高水平扩增分别导致了p53表达的丧失和Myc表达的上调。因此，裸鼠模型对于追踪前列腺癌侵袭性增加过程中遗传变化的克隆进化以及可能克隆与前列腺癌进展相关的基因非常有用。
