Gene amplification and overexpression of PRDM14 in breast cancers
Gene amplification and overexpression of PRDM14 in breast cancers
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DOI：
10.1158/0008-5472.can-06-4111
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发表时间：
2007-10-15
期刊：
影响因子：
11.2
通讯作者：
Tokino, Takashi
中科院分区：
文献类型：
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作者：
Nishikawa, Noriko;Toyota, Minoru;Tokino, Takashi
编码PR（PRDI-BF 1和RIZ）结构域蛋白（PRDM）的几个基因与人类癌症有关。为了探讨PR结构域家族基因在乳腺癌发生中的作用，我们使用半定量实时PCR检测了一组乳腺癌细胞系和原发性乳腺癌标本中PRDM基因家族16个成员的表达谱。我们发现PRDM 14 mRNA在大约三分之二的乳腺癌中过表达;此外，免疫组化分析显示PRDM 14蛋白的表达也上调。基因拷贝数的分析显示，PRDM 14是染色体8 q13上基因扩增的靶点，该区域是在各种人类肿瘤中经常检测到基因扩增的区域。将PRDM 14引入癌细胞增强了细胞生长并降低了它们对化疗药物的敏感性。相反，通过siRNA敲低PRDM 14诱导乳腺癌细胞凋亡，并增加其对化疗药物的敏感性，这表明PRDM 14的上调表达可能在乳腺癌细胞的增殖中起重要作用。PRDM 14在非癌组织中很少或没有表达表明PRDM 14可能是治疗乳腺癌的理想治疗靶点。
Several genes that encode PR (PRDI-BF1 and RIZ) domain proteins (PRDM) have been linked to human cancers. To explore the role of the PR domain family genes in breast carcinogenesis, we examined the expression profiles of 16 members of the PRDM gene family in a panel of breast cancer cell lines and primary breast cancer specimens using semiquantitative real-time PCR. We found that PRDM14 mRNA is overexpressed in about two thirds of breast cancers; moreover, immunohistochemical analysis showed that expression of PRDM14 protein is also up-regulated. Analysis of the gene copy number revealed that PRDM14 is a target of gene amplification on chromosome 8q13, which is a region where gene amplification has frequently been detected in various human tumors. Introduction of PRDM14 into cancer cells enhanced cell growth and reduced their sensitivity to chemotherapeutic drugs. Conversely, knockdown of PRDM14 by siRNA induced apoptosis in breast cancer cells and increased their sensitivity to chemotherapeutic drugs, suggesting that up-regulated expression of PRDM14 may play an important role in the proliferation of breast cancer cells. That little or no expression of PRDM14 is seen in noncancerous tissues suggests that PRDM14 could be an ideal therapeutic target for the treatment of breast cancer.