Model Checking of a Diabetes-Cancer Model
Haijun Gong, Paolo Zuliani, Edmund M. Clarke, Tuan D. Pham, Xiaobo Zhou, Hiroshi L. TANAKA, Mayumi Oyama-Higa, Xiaoyi Jiang, Changming Sun, Jeanne Kowalski, Xiuping Jia · AIP conference proceedings · 2011
Accumulating evidence suggests that cancer incidence might be associated with diabetes mellitus, especially Type II diabetes which is characterized by hyperinsulinaemia, hyperglycaemia, obesity, and overexpression of multiple WNT pathway components. These diabetes risk factors can activate a number of signaling pathways that are important in the development of different cancers. To systematically understand the signaling components that link diabetes and cancer risk, we have constructed a single‐cell, Boolean network model by integrating the signaling pathways that are influenced by these risk factors to study insulin resistance, cancer cell proliferation and apoptosis. Then, we introduce and apply the Symbolic Model Verifier (SMV), a formal verification tool, to qualitatively study some temporal logic properties of our diabetes‐cancer model. The verification results show that the diabetes risk factors might not increase cancer risk in normal cells, but they will promote cell proliferation if the cell is in a precancerous or cancerous stage characterized by losses of the tumor‐suppressor proteins ARF and INK4a.