综述

突变型p53与其合成致死基因的研究进展

展开
  • 1. 昆明理工大学生命科学与技术学院,昆明 650500;
    2. 昆明理工大学医学院,衰老与肿瘤分子遗传学实验室,昆明 650500
刘同阳,硕士研究生,专业方向:肿瘤药理学。E-mail: sunshine_tongyang@163.com

收稿日期: 2014-08-18

  网络出版日期: 2014-12-08

基金资助

国家自然科学基金项目(编号:81260501,U1202221)资助

Synthetic lethal genes to mutant p53

Expand
  • 1. School of Life Science and Biotechnology, Kunming University of Science and Technology, Kunming 650500, China;
    2. Laboratory of Molecular Genetics of Aging and Tumor, Medical College of Kunming University of Science and Technology, Kunming 650500, China

Received date: 2014-08-18

  Online published: 2014-12-08

摘要

恶性肿瘤的靶向治疗已经成为现阶段肿瘤治疗的热点。随着人们对癌基因认知的加深,借助合成致死的方法靶向治疗肿瘤已成为针对肿瘤特异性治疗的新策略。p53基因突变在肿瘤的形成和发展过程中具有重要作用。因此,了解肿瘤中与突变型p53基因有合成致死关系的靶基因的作用方式,有助于指导由突变型p53基因诱发肿瘤的个性化治疗。与突变型p53基因具有合成致死关系的靶基因可分为细胞周期调控基因和细胞非周期调控基因,文章综述了这两类靶基因与突变型p53基因如何构成合成致死作用以及此作用的现实意义。

本文引用格式

刘同阳,郭海强,朱美妍,黄英泽,贾舒婷,罗瑛,张继虹 . 突变型p53与其合成致死基因的研究进展[J]. 遗传, 2015 , 37(4) : 321 -326 . DOI: 10.16288/j.yczz.14-277

Abstract

Targeted therapy has become a powerful approach for cancer treatment. Better understanding of oncogenes as well as synthetic lethal interactions with oncogenes will lead to new strategies for tumor-specific treatment. It is well known that mutant p53 plays an important role in tumorigenesis and tumor development. Thus, understanding the synthetic lethal relationship between p53 mutations and interacting genes in tumor is critical for the personalized treatments of p53 mutant tumors. Synthetic lethal genes to mutant p53 can be divided into cell cycle regulators and non-cell cycle regulators. This paper review show these two types of target genes contribute to synthetic lethal interactions with p53 mutations and potential applications of these interactions in anticancer therapy.

参考文献

[1] Dörr JR, Yu Y, Milanovic M, Beuster G, Zasada C, Däbritz JH, Lisec J, Lenze D, Gerhardt A, Schleicher K, Kratzat S, Pürfurst B, Walenta S, Mueller-Klieser W, Gräler M, Hummel M, Keller U, Buck AK, Dörken B, Willmitzer L, Reimann M, Kempa S, Lee S, Schmitt CA. Synthetic lethal metabolic targeting of cellular senescence in cancer therapy. Nature , 2013, 501(7467): 421-425.
[2] Chan DA, Giaccia AJ. Harnessing synthetic lethal interactions in anticancer drug discovery. Nat Rev Drug Discov , 2011, 10(5): 351-364.
[3] Pessetto ZY, Yan Y, Bessho T, Natarajan A. Inhibition of BRCT(BRCA1)-phosphoprotein interaction enhances the cytotoxic effect of olaparib in breast cancer cells: a proof of concept study for synthetic lethal therapeutic option. Breast Cancer Res Treat , 2012, 134(2): 511-517.
[4] Dietlein F, Thelen L, Jokic M, Jachimowicz RD, Ivan L, Knittel G, Leeser U, Van Oers J, Edelmann W, Heukamp LC, Reinhardt HC. A functional cancer genomics screen identifies a druggable synthetic lethal interaction between MSH3 and PRKDC . Cancer Discov , 2014, 4(5): 592-605.
[5] Warrener P, Kim S, Williams SM, Biery M, Gordon M, Toniatti C, Cleary MA, Linsley PS, Carleton M. Synthetic lethality of PARP inhibition in BRCA-network disrupted tumor cells is associated with interferon pathway activation and enhanced by interferon-γ. Apoptosis , 2012, 17(7): 691-701.
[6] Chan SL, Mok T. PARP inhibition in BRCA-mutated breast and ovarian cancers. Lancet , 2010, 376(9737): 211-213.
[7] Eliyahu D, Michalovitz D, Eliyahu S, Pinhasi-Kimhi O, Oren M. Wild-type p53 can inhibit oncogene-mediated focus formation. Proc Natl Acad Sci USA , 1989, 86(22): 8763-8767.
[8] Steele RJ, Lane DP. P53 in cancer: a paradigm for modern management of cancer. Surgeon , 2005, 3(3): 197-205.
[9] Nigro JM, Baker SJ, Preisinger AC, Jessup JM, Hostetter R, Cleary K, Bigner SH, Davidson N, Baylin S, Devilee P, Glover T, Collins FS, Weslon A, Modali R, Harris CC, Vogelstein B. Mutations in the p53 gene occur in diverse human tumour types. Nature , 1989, 342(6250): 705-708.
[10] Donehower LA, Harvey M, Slagle BL, Mcarthur MJ, Montgomery CA, Jr., Butel JS, Bradley A. Mice deficient for p53 are developmentally normal but susceptible to spontaneous tumours. Nature , 1992, 356(6366): 215-221.
[11] Vousden KH, Lu X. Live or let die: the cell's response to p53. Nat Rev Cancer , 2002, 2(8): 594-604.
[12] Liu J, Zhang C, Feng Z. Tumor suppressor p53 and its gain-of-function mutants in cancer. Acta Biochim Biophys Sin (Shanghai) , 2014, 46(3): 170-179.
[13] Kastan MB, Berkovich E. p53: a two-faced cancer gene. Nat Cell Biol , 2007, 9(5): 489-491.
[14] Dasika GK, Lin SC, Zhao S, Sung P, Tomkinson A, Lee EY. DNA damage-induced cell cycle checkpoints and DNA strand break repair in development and tumorigenesis. Oncogene , 1999, 18(55): 7883-7899.
[15] Wang Q, Fan S, Eastman A, Worland PJ, Sausville EA, O'connor PM. UCN-01: a potent abrogator of G2 checkpoint function in cancer cells with disrupted p53. J Natl Cancer Inst , 1996, 88(14): 956-965.
[16] Rowley R, Hudson J, Young PG. The wee1 protein kinase is required for radiation-induced mitotic delay. Nature , 1992, 356(6367): 353-355.
[17] Hirai H, Iwasawa Y, Okada M, Arai T, Nishibata T, Kobayashi M, Kimura T, Kaneko N, Ohtani J, Yamanaka K, Itadani H, Takahashi-Suzuki I, Fukasawa K, Oki H, Nambu T, Jiang J, Sakai T, Arakawa H, Sakamoto T, Sagara T, Yoshizumi T, Mizuarai S, Kotani H. Small-molecule inhibition of Wee1 kinase by MK-1775 selectively sensitizes p53-deficient tumor cells to DNA-damaging agents. Mol Cancer Ther , 2009, 8(11): 2992-3000.
[18] Wang Y, Decker SJ, Sebolt-Leopold J. Knockdown of Chk1, Wee1 and Myt1 by RNA interference abrogates G2 checkpoint and induces apoptosis. Cancer Biol Ther , 2004, 3(3): 305-313.
[19] Van Linden AA, Baturin D, Ford JB, Fosmire SP, Gardner L, Korch C, Reigan P, Porter CC. In
文章导航

/