Ray Michael E, Yang Zeng Quan, Albertson Donna, Kleer Celina G, Washburn Joseph G, Macoska Jill A, Ethier Stephen P
Department of Radiation Oncology, University of Michigan Medical School, Ann Arbor, Michigan 48109-0948, USA.
Cancer Res. 2004 Jan 1;64(1):40-7. doi: 10.1158/0008-5472.can-03-1022.
Gene amplification is an important mechanism of oncogene activation in breast and other cancers. Characterization of amplified regions of the genome in breast cancer has led to the identification of important oncogenes including erbB-2/HER-2, C-MYC, and fibroblast growth factor receptor (FGFR) 2. Chromosome 8p11-p12 is amplified in 10-15% of human breast cancers. The putative oncogene FGFR1 localizes to this region; however, we show evidence that FGFR inhibition fails to slow growth of three breast cancer cell lines with 8p11-p12 amplification. We present a detailed analysis of this amplicon in three human breast cancer cell lines using comparative genomic hybridization, traditional Southern and Northern analysis, and chromosome 8 cDNA microarray expression profiling. This study has identified new candidate oncogenes within the 8p11-p12 region, supporting the hypothesis that genes other than FGFR1 may contribute to oncogenesis in breast cancers with proximal 8p amplification.
基因扩增是乳腺癌和其他癌症中癌基因激活的重要机制。对乳腺癌基因组扩增区域的特征分析已导致鉴定出包括erbB-2/HER-2、C-MYC和成纤维细胞生长因子受体（FGFR）2在内的重要癌基因。10%至15%的人类乳腺癌中存在8号染色体p11-p12区域的扩增。假定的癌基因FGFR1定位于该区域；然而，我们有证据表明，FGFR抑制并不能减缓三个具有8p11-p12扩增的乳腺癌细胞系的生长。我们使用比较基因组杂交、传统的Southern和Northern分析以及8号染色体cDNA微阵列表达谱分析，对三个人类乳腺癌细胞系中的这个扩增子进行了详细分析。这项研究在8p11-p12区域内鉴定出了新的候选癌基因，支持了这样一种假说，即除FGFR1之外的基因可能在近端8p扩增的乳腺癌的肿瘤发生中起作用。
