Bärlund M, Monni O, Kononen J, Cornelison R, Torhorst J, Sauter G, Kallioniemi A
Laboratory of Cancer Genetics, Institute of Medical Technology, University of Tampere, Finland.
Cancer Res. 2000 Oct 1;60(19):5340-4.
Studies by comparative genomic hybridization imply that amplification of the chromosomal region 17q22-q24 is common in breast cancer. Here, amplification and expression levels of six known genes located at 17q23 were examined in breast cancer cell lines. Four of them (RAD51C, S6K, PAT1, and TBX2) were found to be highly amplified and overexpressed. To investigate the involvement of these genes in vivo, fluorescence in situ hybridization analysis of a tissue microarray containing 372 primary breast cancers was used. S6K, PAT1, and TBX2 were coamplified in about 10% of tumors, whereas RADS1C amplification was seen in only 3% of tumors. Expression analysis in 12 primary tumors showed that RAD51C and S6K were consistently expressed in all cases in which they were amplified and also in some tumors without amplification. These data suggest that 17q23 amplification results in simultaneous up-regulation of several genes, whose increased biological activity may jointly contribute to the more aggressive clinical course observed in patients with 17q23-amplified tumors.
比较基因组杂交研究表明，17q22 - q24染色体区域的扩增在乳腺癌中很常见。在此，对位于17q23的六个已知基因在乳腺癌细胞系中的扩增和表达水平进行了检测。发现其中四个基因（RAD51C、S6K、PAT1和TBX2）高度扩增且过表达。为了研究这些基因在体内的作用，对包含372例原发性乳腺癌的组织芯片进行了荧光原位杂交分析。S6K、PAT1和TBX2在约10%的肿瘤中共同扩增，而RADS1C扩增仅在3%的肿瘤中可见。对12例原发性肿瘤的表达分析表明，RAD51C和S6K在所有扩增病例以及一些未扩增的肿瘤中均持续表达。这些数据表明，17q23扩增导致多个基因同时上调，其生物学活性的增加可能共同促成了17q23扩增肿瘤患者中观察到的更具侵袭性的临床病程。
