Daino Kazuhiro, Roch-Lefevre Sandrine, Ugolin Nicolas, Altmeyer-Morel Sandrine, Guilly Marie-Noëlle, Chevillard Sylvie
LCE/iRCM/DSV/CEA, 92265 Fontenay-aux-Roses Cedex, France.
Biochem Biophys Res Commun. 2009 Dec 18;390(3):654-8. doi: 10.1016/j.bbrc.2009.10.022. Epub 2009 Oct 13.
We have previously studied genomic copy number changes and global gene expression patterns in rat osteosarcomas (OS) induced by the bone-seeking alpha emitter (238)Pu by comparative genomic hybridization (CGH) and oligonucleotide microarray analyses, respectively. Among the previously identified genes that were down-regulated in radiation-induced rat OS tumors, Cited2 (Cbp/p300-interacting transactivator, with Glu/Asp-rich carboxy-terminal domain, 2) and Akap12 (a kinase anchoring protein, also known as src-suppressed C-kinase substrate, SSeCKS) genes mapped to the most frequently lost regions on chromosome 1p. In the present study, relative copy number losses of Cited2 and Akap12 genes were observed in 8 of 15 (53%) and 10 of 15 (67%) tumors by quantitative PCR analysis. Loss of Cited2 and Akap12 in the tumors was confirmed at the levels of mRNA and protein expression by quantitative RT-PCR and immunoblot analyses, respectively. These results indicate that Cited2 and Akap12 are silenced in radiation-induced OS, and therefore are novel candidate tumor-suppressor genes of this tumor.
我们之前分别通过比较基因组杂交（CGH）和寡核苷酸微阵列分析，研究了亲骨性α发射体（238）Pu诱导的大鼠骨肉瘤（OS）中的基因组拷贝数变化和全局基因表达模式。在先前鉴定出的在辐射诱导的大鼠OS肿瘤中下调的基因中，Cited2（Cbp/p300相互作用反式激活因子，富含Glu/Asp的羧基末端结构域，2）和Akap12（一种激酶锚定蛋白，也称为src抑制的C激酶底物，SSeCKS）基因定位于1号染色体p臂上最常缺失的区域。在本研究中，通过定量PCR分析，在15个肿瘤中的8个（53%）和15个肿瘤中的10个（67%）中观察到Cited2和Akap12基因的相对拷贝数缺失。分别通过定量RT-PCR和免疫印迹分析，在mRNA和蛋白质表达水平上证实了肿瘤中Cited2和Akap12的缺失。这些结果表明，Cited2和Akap12在辐射诱导的OS中沉默，因此是该肿瘤新的候选抑癌基因。
