Mathematical Model of a Telomerase Transcriptional Regulatory Network Developed by Cell-Based Screening: Analysis of Inhibitor Effects and Telomerase Expression Mechanisms
Figure 3
Modelling inhibitor effects on the TERT transcriptional neighbourhood.
A2780 cells were transfected with each luciferase reporter shown and 32(A), 5 µM SU6656, (B), 10 µM FR180204. Left panels show mean ± SEM of 3 experiments (ns: not significant; *: p<0.5; **: p<0.01). Central panels: luciferase assay results meeting model cut-off of FC>1.5, p<0.01 were modelled as rule table modifications. Heat-map representation of new model steady states obtained by setting rule tables for constitutive activation or suppression at those nodes significantly affected in the luciferase assay. Red colour indicates the node is on, green colour indicates the node is off. Right panels: analysis of TERT expression after repeat inhibitor treatments. Control and treated samples from treatment time points shown were analysed by RT-QPCR for TERT expression normalised to RPS15. Mean ± SEM of TERT expression in treated cells relative to control from three experiments (ns: not significant; **: p<0.01).