Oncogene-tumor suppressor gene feedback interactions and their control

  • Received: 01 September 2014 Accepted: 29 June 2018 Published: 01 August 2015
  • MSC : Primary: 92B05, 92C42; Secondary: 34C23.

  • We propose the hypothesis that for a particular type of cancer there exists a key pair of oncogene (OCG) and tumor suppressor gene (TSG) that is normally involved in strong stabilizing negative feedback loops (nFBLs) of molecular interactions, and it is these interactions that are sufficiently perturbed during cancer development. These nFBLs are thought to regulate oncogenic positive feedback loops (pFBLs) that are often required for the normal cellular functions of oncogenes. Examples given in this paper are the pairs of MYC and p53, KRAS and INK4A, and E2F1 and miR-17-92. We propose dynamical models of the aforementioned OCG-TSG interactions and derive stability conditions of the steady states in terms of strengths of cycles in the qualitative interaction network. Although these conditions are restricted to predictions of local stability, their simple linear expressions in terms of competing nFBLs and pFBLs make them intuitive and practical guides for experimentalists aiming to discover drug targets and stabilize cancer networks.

    Citation: Baltazar D. Aguda, Ricardo C.H. del Rosario, Michael W.Y. Chan. Oncogene-tumor suppressor gene feedback interactions and their control[J]. Mathematical Biosciences and Engineering, 2015, 12(6): 1277-1288. doi: 10.3934/mbe.2015.12.1277

    Related Papers:

  • We propose the hypothesis that for a particular type of cancer there exists a key pair of oncogene (OCG) and tumor suppressor gene (TSG) that is normally involved in strong stabilizing negative feedback loops (nFBLs) of molecular interactions, and it is these interactions that are sufficiently perturbed during cancer development. These nFBLs are thought to regulate oncogenic positive feedback loops (pFBLs) that are often required for the normal cellular functions of oncogenes. Examples given in this paper are the pairs of MYC and p53, KRAS and INK4A, and E2F1 and miR-17-92. We propose dynamical models of the aforementioned OCG-TSG interactions and derive stability conditions of the steady states in terms of strengths of cycles in the qualitative interaction network. Although these conditions are restricted to predictions of local stability, their simple linear expressions in terms of competing nFBLs and pFBLs make them intuitive and practical guides for experimentalists aiming to discover drug targets and stabilize cancer networks.


    加载中
    [1] Curr Drug Discov Technol., 10 (2013), 125-138.
    [2] in Molecular Diagnostics and Therapy of Pancreatic Cancer (ed. A. Azmi), Elsevier Academic Press, (2014), 281-296.
    [3] PLoS Comput Biol., 3 (2007), 1674-1678.
    [4] Biophys J., 101 (2011), 2082-2091.
    [5] Proc Natl Acad Sci USA, 105 (2008), 19678-19683.
    [6] Nat Rev Cancer, 9 (2009), 415-428.
    [7] Nature, 494 (2013), p506.
    [8] Nature, 511 (2014), 543-550.
    [9] J Thorac Dis., 5 (2013), S479-S490.
    [10] J Clin Invest., 122 (2012), 1519-1528.
    [11] ACM Trans Math Softw (TOMS), 29 (2003), 141-164.
    [12] Cell, 139 (2009), 654-656.
    [13] Nat Rev Cancer, 4 (2004), 177-183.
    [14] Oral Oncol, 45 (2009), 335-339.
    [15] http://cancer.sanger.ac.uk/cancergenome/projects/census/" target="_blank">http://cancer.sanger.ac.uk/cancergenome/projects/census/
    [16] (network of cancer genes).
    [17] Nature, 502 (2013), 333-339.
    [18] Clin Chest Med., 32 (2011), 703-740.
    [19] Cold Spring Harb Perpect Biol., 2 (2010), a003236.
    [20] PLoS One, 6 (2011), e26302.
    [21] Cell Death Dis., 5 (2014), e1032.
    [22] Cancer Cell, 5 (2004), 311-316.
    [23] PLoS Genet., 7 (2011), e1002135.
    [24] Nucleic Acids Res., 34 (2006), 1745-1754.
    [25] J Clin Pathol., 59 (2006), 445-4453.
    [26] Gut., 60 (2011), 116-129.
    [27] Nat Rev Cancer, 10 (2010), 59-64.
    [28] Oncogene, 34 (2015), 314-322.
    [29] Apoptosis, 16 (2011), 950-958.
    [30] Sci Rep., 3 (2013), p2650.
    [31] Best Pract Res Clin Gastroenterol, 20 (2006), 651-674.
  • Reader Comments
  • © 2015 the Author(s), licensee AIMS Press. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0)
通讯作者: 陈斌, bchen63@163.com
  • 1. 

    沈阳化工大学材料科学与工程学院 沈阳 110142

  1. 本站搜索
  2. 百度学术搜索
  3. 万方数据库搜索
  4. CNKI搜索

Metrics

Article views(1898) PDF downloads(1212) Cited by(1)

Article outline

/

DownLoad:  Full-Size Img  PowerPoint
Return
Return

Catalog