1962年在肺癌胸水渗出液中发现并报道了一种特殊的染色体外小体结构,后来这种结构被命名为双微体(double minute chromosomes, DMs)。双微体是染色体外基因扩增的标志物,是无着丝粒、无端粒、可自主复制的成对小体,多携带癌基因和耐药基因,与肿瘤发展演进以及肿瘤耐药密切相关。

、研究概况

本研究室从1998年开始双微体结构和功能的研究,是目前国内唯一进行双微体系统生物学研究的实验室。从双微体的超微结构、分子结构,到相关基因的功能等,对双微体的结构特征和序列功能进行分析,以揭示双微体的发生机制,探索双微体与肿瘤以及肿瘤耐药的关联。

、研究内容

1、双微体超微结构研究

2、不同组织来源实体肿瘤中双微体扩增子的起源、序列及结构比较分析

3、双微体携带扩增基因功能及相关信号通路。

4、实体肿瘤耐药性获得过程中双微体的形成和演化机制研究。

三、发表学术文章(*通讯作者)

  1. Yu L, Zhao Yan, Quan C, Ji W, Zhu J, Huang Y, Guan R, Sun D, Jin Y, Meng X, Zhang C, Yu Y, Bai J, Sun W, and Fu S*. Gemcitabine eliminates double minute chromosomes from human ovarian cancer cells. Plos One. 2013 July 6 (Accepted)
  2. Zhu J, Yu Y, Meng X, Fan Y, Zhang Y, Zhou C, Yue Z, Jin Y, Zhang C, Yu L, Ji W, Jia X, Guan R, Wu J, Yu J, Bai J, Guan XY, Wang M, Lee KY, Sun W, and Fu S*.  (2013) De novo-generated small palindromes are characteristic of amplicon boundary junction of double minutes. Int J Cancer. 133(4):797-806. PMID: 23382041
  3. Jin Y, Liu Z, Cao W, Ma X, Fan Y, Yu Y, Bai J, Chen F, Rosales J, Lee KY, and Fu S*. (2012) Novel functional MAR elements of double minute chromosomes in human ovarian cells capable of enhancing gene expression. PLoS One. 7(2):e30419. PMID: 22319568
  4. Fan Y, Mao R, Lv H, Xu J, Yan L, Liu Y, Shi M, Ji G, Yu Y, Bai J, Jin Y, and Fu S*. (2011) Frequency of double minute chromosomes and combined cytogenetic abnormalities and their characteristics. J Appl Genet. 52(1):53-9. PMID: 21107781
  5. Kong F, Zhu J, Wu J, Peng J, Wang Y, Wang Q, Fu S, Yuan LL, and Li T. (2011) dbCRID: a database of chromosomal rearrangements in human diseases. Nucleic Acids Res. 39(Database issue):D895-900. PMID: 21051346
  6. Fan Y, Mao R, Bai J, Zhang X, Lei Q, Fu S*. (2008) AFM images of G1-phase premature condensed chromosomes:Evidence for 30 nm changed to 50 nm chromatin fibers. Applied Surface Science. 254(6):1676-83.
  7. Fan Y, Zhang X, Bai J, Mao R, Zhang C, Lei Q, Fu S*. (2007) Ultrastructural organization of premature condensed chromosomes at S-phase as observerd by atomic force microscopy. Applied Surface Science. 253(12):5281-6.
  8. Zhang CY, Feng YX, Yu Y, Sun WJ, Bai J, Chen F, Fu SB*. (2006) The molecular mechanism of resistance to methotrexate in mouse methotrexate-resistant cells by cancer drug resistance and metabolism SuperArray. Basic Clin Pharmacol Toxicol. 99(2):141-5. PMID: 16918715
  9. Deng X, Zhang L, Zhang Y, Yan Y, Xu Z, Dong S, and Fu S*. (2006) Double minute chromosomes in mouse methotrexate-resistant cells studied by atomic force microscopy. Biochem Biophys Res Commun, 346(4):1228-33. PMID: 16806082
  10. Feng YX, Bai J, Zhang CY, Fu SB*. (2006) Proteomic analysis for the identification of proteins related to methotrexate resistance. Yi Chuan Xue Bao. 33(5):391-6. PMID: 16722333
  11. 张钰,邓新宇,白静,李璞,傅松滨*. (2006) 人卵巢癌细胞及小鼠MTX抗性细胞中DMs大小的测定. 国际遗传学杂志, 29(4): 241-5.
  12. 邓新宇,张钰,曾力,国立秋,闫永达,董申,张贵寅,李璞,傅松滨*.2003)原子力显微镜在双微体形态学研究中的应用. 遗传学报, 30(9):881-5. PMID: 14577382