Oncogene-tumor suppressor gene feedback interactions and their control

Baltazar D.  Aguda; Ricardo C.H. del  Rosario; Michael W.Y.  Chan

doi:10.3934/mbe.2015.12.1277

Article Contents

2015, Volume 12, Issue 6: 1277-1288. Doi: 10.3934/mbe.2015.12.1277

This issue Previous Article Dynamics and control of a mathematical model for metronomic chemotherapy Next Article Algebraic and topological indices of molecular pathway networks in human cancers

Oncogene-tumor suppressor gene feedback interactions and their control

1.
DiseasePathways LLC, Bethesda, Maryland, 20814
2.
Computational and Systems Biology, Genome Institute of Singapore, 60 Biopolis St., #02-01 Genome, 138672
3.
Department of Life Science & Institute of Molecular Biology, National Chung Cheng University, Min-Hsiung, China-Yi

Received: September 2014

Revised: March 2015

Published: August 2015

Abstract / Introduction Related Papers Cited by

Abstract

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.

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Mathematics Subject Classification: Primary: 92B05, 92C42; Secondary: 34C23.

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