抑癌基因ARID1A在肿瘤中的研究进展.pdf

中国细胞生物学学报 Chinese Journal of Cell Biology 2014, 36(1): 128– 134 DOI: 10.11844/cj cb.2014.01.02 17 ARID1A 抑癌基因 在肿瘤中的研究进展 张 倩 颜海波 刘 锋* (复旦大学生物医学研究院, 上海200032) 摘要 染色质重塑复合物相关基因在癌症中频繁突变, 这种现象逐渐引起研究者的重视。然 而, 染色质重塑活动如何引起癌症发生, 对此机理研究甚少。ARID 1A是SWI/SNF(BRG1相关因子) 染色质重塑复合物中的一个亚基, 具有DNA结合活性, 可以与富含AT的DNA序列特异性结合。近 来基因组测序发现, ARID 1A在卵巢癌、肝癌、胃癌、乳腺癌等肿瘤中频繁发生突变, 这些突变导 ARID1A 致ARID 1A在肿瘤中表达降低, 表明 是个潜在的抑癌基因。该文将针对ARID 1A在各种癌 症中的缺失及失活机制、ARID 1A 的生物学功能和潜在抑癌机理以及与临床预后之间关系等方面 做一综述, 以期为肿瘤诊断、治疗提供新思路。 关键词 ARID 1A; SWI/SNF; 肿瘤抑癌基因; PI3K Tumor Suppressor Gene ARID1A in Cancers Zhang Qian, Yan Haibo, Liu Feng* (Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China) Abstract Chromatin remodeling complex genes are found to be frequently mutated in a variety of human cancers. However, the mechanisms by which chromatin remodeling complexes contribute to the cancer phenotype are poorly understood. ARID1A (AT-rich interactive domain-containing protein 1A) is a large subunit of SWI/SNF (BRG1-associated factors) chromatin remodeling complex. ARID1A has a DNA-binding domain that can specifi- cally bind an AT-rich DNA sequence. Recent exome sequencing studies reveal that ARID1A is frequently mutated in carcinomas, including ovarian, liver, gastric and breast cancers. These mutations cause the reduced expression of ARID1A in cancers, which indicates that ARID1A might be a tumor suppressor. Here, we review recent studies of ARID1A mutation and low expression in cancers. We summarize the novel findings on the biological functions and the regulatory tumor-suppressing mechanisms of AR