Molecular characterization of the t(3;9) associated with immortalization in the MCF10A cell line
Molecular characterization of the t(3;9) associated with immortalization in the MCF10A cell line
复制标题
DOI：
10.1016/j.cancergencyto.2005.04.019
复制
发表时间：
2005-11-01
影响因子：
--
通讯作者：
Matsui, S
中科院分区：
文献类型：
--
作者：
Cowell, JK;LaDuca, J;Matsui, S
t（3; 9）（p14; p21）是伴随从原代培养到永生化细胞系的单一细胞遗传学事件，提示其与永生化表型的形成有关。为了研究这种重排中断点的分子后果，我们使用了荧光原位杂交（FISH）和阵列比较基因组杂交（CGH）的组合。3 p14易位断裂点发生在BAC RP 11 - 795 e22内，其仅容纳TA-FA 1基因，TA-FA 1基因是一种被认为参与细胞因子信号传导的新型富含半胱氨酸的分泌蛋白。TA-FA 1在正常乳腺组织中表达，而在MCF 10A中不表达，并且在一系列乳腺癌细胞系中显示差异表达。9 p易位断裂点导致衍生染色体9上约4兆碱基的缺失，其包括CDKN 2A（p，16）基因。阵列CGH和FISH分析表明，BAC 149 i22，其中包含CDKN 2A/B基因，也删除了明显的正常拷贝的9号染色体上，使MCF 10 A无效的p16/p15基因。涉及染色体1 q、5 q和8 q的重排所导致的染色体区域的增益和损失的确切程度也已经使用BAC阵列表征。(c)2005年爱思唯尔公司All rights reserved.
The t(3;9)(p14;p21) in the MCF10A human mammary gland epithelial cell line was the single cytogenetic event that accompanied the transition from primary culture to immortalized cell line, suggesting that it is related to the development of the immortalization phenotype. To study the molecular consequences of the breakpoints in this rearrangement, we used a combination of fluorescence in situ hybridization (FISH) and array comparative genomic hybridization (CGH). The 3p14 translocation breakpoint occurs within BAC RP11-795e22, which accommodates only the TA-FA1 gene, a novel cysteine-rich secreted protein thought to be involved in cytokine signaling. TA-FA1 is expressed in normal breast tissue, not in MCF10A, and shows differential expression in a range of breast cancer cell lines. The 9p translocation breakpoint results in a deletion of approximately 4 megabases on the derivative chromosome 9, which includes the CDKN2A (p,16) gene. Array CGH and FISH analysis demonstrated that BAC 149i22, which contains the CDKN2A/B genes, is also deleted specifically on the apparently normal copy of chromosome 9, making MCF10A null for the p16/p15 genes. The exact extent of gains and losses of chromosome regions resulting from rearrangements involving chromosomes 1q, 5q, and 8q have also been characterized using the BAC arrays. (c) 2005 Elsevier Inc. All rights reserved.