Synergistic effect of Bcl2, Myc and Ccnd1 transforms mouse primary B cells into malignant cells
Synergistic effect of Bcl2, Myc and Ccnd1 transforms mouse primary B cells into malignant cells
复制标题
DOI：
10.3324/haematol.2011.041053
复制
发表时间：
2011-09-01
期刊：
影响因子：
--
通讯作者：
Seto, Masao
中科院分区：
文献类型：
--
作者：
Nakagawa, Masao;Tsuzuki, Shinobu;Seto, Masao
背景BCL 2和MYC或MYC和CCND1的组合产生的协同效应已经涉及人类B细胞淋巴瘤。虽然其他合作基因的鉴定是重要的，我们目前对这些基因的了解仍然很少。本研究的目的是鉴定与BCL 2和MYC或MYC和CCND1相关的其他合作基因。首先，我们评估了Bcl 2、Myc和Ccnd1是否可以合作。接下来，我们开发了一种基于协同作用的功能筛选方法，用于鉴定与Bcl 2和Myc.Design和MethodsGrowth的其他癌基因（S），在培养中，集落形成和致癌性在体内进行了评估，在小鼠原发性B细胞外源表达Bcl 2，Myc和Ccnd1的各种组合。为了进行功能筛选，用逆转录病毒cDNA文库感染表达Bcl 2和Myc的原代B细胞。插入的cDNA的转化细胞在culture.ResultsPrimary B细胞外源性表达Bcl 2，Myc和Ccnd1表现出因子独立的生长能力，增强的集落形成能力和侵略性致癌性，不同的情况下观察到的任何组合，只有两个基因的表达。结论Bcl2、Myc和Ccnd1或Bcl2、Myc和CCND3协同作用可使小鼠原代B细胞向侵袭性恶性细胞转化。我们的新的基于协同作用的方法对于识别肿瘤发展中的协同基因组合是有用的，并且可以扩展我们对广泛的致癌元素的系统理解。
BackgroundA synergistic effect resulting from a combination of BCL2 and MYC or MYC and CCND1 has been implicated in human B-cell lymphomas. Although the identification of other cooperative genes involved is important, our present understanding of such genes remains scant. The objective of this study was to identify the additional cooperative gene(s) associated with BCL2 and MYC or MYC and CCND1. First, we assessed whether Bcl2, Myc and Ccnd1 could cooperate. Next, we developed a synergism-based functional screening method for the identification of other oncogene(s) that act with Bcl2 and Myc.Design and MethodsGrowth in culture, colony formation and oncogenicity in vivo were assessed in mouse primary B cells exogenously expressing various combinations of Bcl2, Myc and Ccnd1. For the functional screening, Bcl2- and Myc-expressing primary B cells were infected with a retroviral cDNA library. Inserted cDNA of transformed cells in culture were then identified.ResultsPrimary B cells exogenously expressing Bcl2, Myc and Ccnd1 showed factor-independent growth ability, enhanced colony-forming capability and aggressive oncogenicity, unlike the cases observed with the expression of any combination of only two of the genes. We identified CCND3 and NRAS as cooperative genes with Bcl2 and Myc through the functional screening.ConclusionsBcl2, Myc and Ccnd1 or Bcl2, Myc and CCND3 synergistically transformed mouse primary B cells into aggressive malignant cells. Our new synergism-based method is useful for the identification of synergistic gene combinations in tumor development, and may expand our systemic understanding of a wide range of cancer-causing elements.