Sarraf Shireen, Tejada Raphael, Abawi Massih, Oberst Michael, Dennis Tom, Simon Kelly Claire, Blancato Jan
Department of Oncology, Georgetown University, 3800 Reservoir Road NW, Washington, DC 20007, USA.
Cancer Genet Cytogenet. 2005 Aug;161(1):63-9. doi: 10.1016/j.cancergencyto.2005.01.003.
Cell lines derived from tumors contain numerous chromosomal aberrations and are the focus of study in tumor evolution. The ovarian teratocarcinoma cell line PA-1 demonstrates a single chromosomal aberration: a reciprocal t(15;20)(p11.2;q11.2). A complete molecular genetic analysis was undertaken to characterize this cell line. The PA-1 cell line was studied with fluorescence in situ hybridization (FISH), spectral karyotyping (SKY), bacterial artificial chromosome (BAC) microarray, and Western blotting. Amplification of 20q is frequently implicated in both breast and ovarian cancer; this region contains a number of oncogenes including MDM2, ZNF217, and the ovarian tumor marker WFDC2 (alias HE4). FISH revealed gene amplification of AIB1 (now known as NCOA3) but not STK15 (now known as AURKA). Immunoblot analysis demonstrated 3.6-fold overexpression of the AIB1 protein product, but no elevation of the STK15. BAC cancer gene microarray analysis showed gene amplification of > or =1.20 for five oncogenes. The presence of a consistent single change in PA-1, the t(15;20)(p11.2;q11.2), suggests that the aberration is significant with respect to the transformation status of the cell line. This translocation appears to cause overexpression of AIB1 (and perhaps other proteins), which may provide an immortalizing effect on this cell line.
源自肿瘤的细胞系含有大量染色体畸变,是肿瘤进化研究的重点。卵巢畸胎癌细胞系PA-1表现出单一的染色体畸变:相互易位t(15;20)(p11.2;q11.2)。进行了完整的分子遗传学分析以表征该细胞系。使用荧光原位杂交(FISH)、光谱核型分析(SKY)、细菌人工染色体(BAC)微阵列和蛋白质免疫印迹法对PA-1细胞系进行了研究。20q的扩增在乳腺癌和卵巢癌中都经常涉及;该区域包含许多癌基因,包括MDM2、ZNF217和卵巢肿瘤标志物WFDC2(别名HE4)。FISH显示AIB1(现称为NCOA3)基因扩增,但STK15(现称为AURKA)未扩增。免疫印迹分析表明AIB1蛋白产物过表达3.6倍,但STK15未升高。BAC癌基因微阵列分析显示五个癌基因的基因扩增倍数≥1.20。PA-1中存在一致的单一变化t(15;20)(p11.2;q11.2),表明该畸变对于该细胞系的转化状态具有重要意义。这种易位似乎导致AIB1(可能还有其他蛋白质)过表达,这可能对该细胞系产生永生化作用。