Analysis of the molecular networks in androgen dependent and independent prostate cancer revealed fragile and robust subsystems.

PloS One
Ryan TasseffJeffrey D Varner

Abstract

Androgen ablation therapy is currently the primary treatment for metastatic prostate cancer. Unfortunately, in nearly all cases, androgen ablation fails to permanently arrest cancer progression. As androgens like testosterone are withdrawn, prostate cancer cells lose their androgen sensitivity and begin to proliferate without hormone growth factors. In this study, we constructed and analyzed a mathematical model of the integration between hormone growth factor signaling, androgen receptor activation, and the expression of cyclin D and Prostate-Specific Antigen in human LNCaP prostate adenocarcinoma cells. The objective of the study was to investigate which signaling systems were important in the loss of androgen dependence. The model was formulated as a set of ordinary differential equations which described 212 species and 384 interactions, including both the mRNA and protein levels for key species. An ensemble approach was chosen to constrain model parameters and to estimate the impact of parametric uncertainty on model predictions. Model parameters were identified using 14 steady-state and dynamic LNCaP data sets taken from literature sources. Alterations in the rate of Prostatic Acid Phosphatase expression was sufficient to ...Continue Reading

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Citations

Mar 26, 2011·Integrative Biology : Quantitative Biosciences From Nano to Macro·Ryan TasseffJeffrey D Varner
Mar 14, 2012·PLoS Computational Biology·Sang Ok SongGilles Clermont
Sep 26, 2012·Annals of Biomedical Engineering·Anirikh ChakrabartiJeffrey D Varner
Jul 29, 2010·Biotechnology Journal·Sang Ok SongJeffrey D Varner
Nov 10, 2013·Cell Communication and Signaling : CCS·Kentaro HayashiKumar Selvarajoo
Nov 21, 2017·PloS One·Adithya SagarJeffrey D Varner
Sep 1, 2012·Molecular Cancer Research : MCR·Miao ZhongShafiq A Khan
Apr 14, 2020·Metabolic Engineering Communications·Nicholas HorvathJeffrey D Varner

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