Yi Yajun, Nandana Srinivas, Case Thomas, Nelson Colleen, Radmilovic Tatjana, Matusik Robert J, Tsuchiya Karen D
Clinical Research Division, Fred Hutchinson Cancer Research Center and Department of Laboratories, Seattle Children's Hospital, WA, USA.
Mol Cytogenet. 2009 Sep 26;2:18. doi: 10.1186/1755-8166-2-18.
The purpose of this study was to identify candidate metastasis suppressor genes from a mouse allograft model of prostate cancer (NE-10). This allograft model originally developed metastases by twelve weeks after implantation in male athymic nude mice, but lost the ability to metastasize after a number of in vivo passages. We performed high resolution array comparative genomic hybridization on the metastasizing and non-metastasizing allografts to identify chromosome imbalances that differed between the two groups of tumors.
This analysis uncovered a deletion on chromosome 2 that differed between the metastasizing and non-metastasizing tumors. Bioinformatics filters were employed to mine this region of the genome for candidate metastasis suppressor genes. Of the 146 known genes that reside within the region of interest on mouse chromosome 2, four candidate metastasis suppressor genes (Slc27a2, Mall, Snrpb, and Rassf2) were identified. Quantitative expression analysis confirmed decreased expression of these genes in the metastasizing compared to non-metastasizing tumors.
This study presents combined genomics and bioinformatics approaches for identifying potential metastasis suppressor genes. The genes identified here are candidates for further studies to determine their functional role in inhibiting metastases in the NE-10 allograft model and human prostate cancer.
本研究的目的是从小鼠前列腺癌同种异体移植模型（NE-10）中鉴定候选转移抑制基因。该同种异体移植模型最初在雄性无胸腺裸鼠植入后12周出现转移，但在多次体内传代后失去了转移能力。我们对转移性和非转移性同种异体移植进行了高分辨率阵列比较基因组杂交，以鉴定两组肿瘤之间不同的染色体失衡。
该分析发现2号染色体上的一个缺失在转移性和非转移性肿瘤之间存在差异。利用生物信息学筛选方法在该基因组区域挖掘候选转移抑制基因。在小鼠2号染色体上感兴趣区域内的146个已知基因中，鉴定出四个候选转移抑制基因（Slc27a2、Mall、Snrpb和Rassf2）。定量表达分析证实，与非转移性肿瘤相比，这些基因在转移性肿瘤中的表达降低。
本研究提出了结合基因组学和生物信息学方法来鉴定潜在的转移抑制基因。这里鉴定出的基因是进一步研究的候选对象，以确定它们在NE-10同种异体移植模型和人类前列腺癌中抑制转移的功能作用。
