Pelliccia Franca, Curatolo Angela, Limongi Zaira M, Bosco Nazario, Rocchi Angela
Dipartimento di Genetica e Biologia Molecolare, Università La Sapienza, P le Aldo Moro 5, 00185, Roma, Italia.
Cancer Genet Cytogenet. 2007 Oct 15;178(2):144-50. doi: 10.1016/j.cancergencyto.2007.07.004.
Common fragile sites (CFSs) are chromosome regions that exhibit gaps and breaks when the cells are exposed to replication stress and to some DNA-binding compounds. In cancer cells, the CFSs are frequently involved in recurrent chromosome rearrangements. Furthermore, altered expression of associated genes, known or potential oncogenes, and tumor-suppressor genes has often been observed. Seventeen of the 88 listed CFSs have been analyzed at the molecular level, but the basis of their fragility has not been clarified. In the present work, the nine genes TGFB2, IARS2, MARK1, TAF1A, TP53BP2, ADPRT, including a very large gene ESRRG and two microRNA genes, MIRN194-1 and MIRN215, localized in the fragile site FRA1H, were investigated by polymerase chain reaction (PCR) for homozygous deletions and by real-time PCR for modification or loss of gene expression in a panel of 19 cancer cell lines. The expression level of five (ESRRG, TGFB2, MIRN194-1, MIRN215, and MARK1) of the nine genes studied presented significant modifications in some of the 19 examined tumor-derived cell lines compared to their normal control tissues. Because of their function, these genes could have a role in neoplastic transformation.
常见脆性位点（CFSs）是染色体区域，当细胞暴露于复制应激和某些DNA结合化合物时，这些区域会出现间隙和断裂。在癌细胞中，CFSs经常参与反复发生的染色体重排。此外，经常观察到相关基因（已知或潜在的癌基因和肿瘤抑制基因）的表达发生改变。在列出的88个CFSs中，有17个已在分子水平上进行了分析，但其脆性的基础尚未阐明。在本研究中，通过聚合酶链反应（PCR）研究了位于脆性位点FRA1H的9个基因，即转化生长因子β2（TGFB2）、异亮氨酰-tRNA合成酶2（IARS2）、微管亲和调节激酶1（MARK1）、TATA框结合蛋白相关因子1A（TAF1A）、p53结合蛋白2（TP53BP2）、腺嘌呤磷酸核糖转移酶（ADPRT），包括一个非常大的基因雌激素相关受体γ（ESRRG）和两个微小RNA基因，即miR-194-1（MIRN194-1）和miR-215（MIRN215），检测其纯合缺失情况，并通过实时PCR检测19种癌细胞系中基因表达的改变或缺失。与正常对照组织相比，所研究的9个基因中的5个（ESRRG、TGFB2、MIRN194-1、MIRN215和MARK1）在19种检测的肿瘤来源细胞系中的某些细胞系中呈现出显著的表达改变。由于它们的功能，这些基因可能在肿瘤转化中发挥作用。
