title: Endogenous molecular-cellular hierarchical modeling of prostate carcinogenesis uncovers robust structure.
abstract: We explored endogenous molecular-cellular network hypothesis for prostate cancer by constructing relevant endogenous interaction network model and analyzing its dynamical properties. Molecular regulations involved in cell proliferation, apoptosis, differentiation and metabolism are included in a hierarchical mathematical modeling scheme. This dynamical network organizes into multiple robust functional states, including physiological and pathological ones. Some states have characteristics of cancer: elevated metabolic and immune activities, high concentration of growth factors and different proliferative, apoptotic and adhesive behaviors. The molecular profile of calculated cancer state agrees with existing experiments. The modeling results have additional predictions which may be validated by further experiment: 1) Prostate supports both stem cell like and liver style proliferation; 2) While prostate supports multiple cell types, including basal, luminal and endocrine cell type differentiated from its stem cell, luminal cell is most likely to be transformed malignantly into androgen independent type cancer; 3) Retinoic acid pathway and C/EBPα are possible therapeutic targets.
authors: GeneMath, 5525 27th Ave. N.E., Seattle, WA 98105, USA.
authors: Xiaomei
authors: X
authors: Zhu
authors: Key Laboratory of Systems Biomedicine, Ministry of Education, Shanghai Center for Systems Biomedicine, Shanghai Jiao Tong University, Shanghai 200240, China; School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai 200240, China. Electronic address: rsyuan.acm06@gmail.com.
authors: Ruoshi
authors: R
authors: Yuan
authors: Institute for Systems Biology, 401 Terry Ave. N., Seattle, WA 98109-5234, USA.
authors: Leroy
authors: L
authors: Hood
authors: Key Laboratory of Systems Biomedicine, Ministry of Education, Shanghai Center for Systems Biomedicine, Shanghai Jiao Tong University, Shanghai 200240, China. Electronic address: aoping@sjtu.edu.cn.
authors: Ping
authors: P
authors: Ao
mesh_terms: D063646:Carcinogenesis; D002454:Cell Differentiation; D049109:Cell Proliferation; D006801:Humans; D008297:Male; D008954:Models, Biological; D009928:Organ Specificity; D011471:Prostatic Neoplasms / Q000473:pathology*
keywords: Attractors; Dynamical System; Endogenous Molecular-cellular Network; Potential Landscape; Prostate Cancer