Figure 6.

Systems view of a cellular state anticipating in vivo innate drug resistance. Molecular interaction networks characteristic of a resistant cellular state, prior to drug exposure, showing an integrated view of networks from resistant cells arrested either in G₁ phase or in S-G₂ phases. The representation recapitulates the dynamics and dependencies of gene modulations with specific components of the cell machinery identified through statistical comparisons, GO annotations and literature mining. Biochemical interactions are specified; the symbols used are derived from the standard nomenclature proposed by CellDesigner v2.5: arrow, direct activation; dotted arrow, unknown interaction; arrow with a strike through it, indirect activation; bar, inhibition; dotted bar, unknown inhibition; dashed arrow, transcriptional activation; dashed bar, transcriptional inhibition; arrow with clear arrowhead, transport. Red and green colors refer to up- and down-regulation, respectively, in resistant versus sensitive states; other genes analyzed with microarrays and/or Q-PCR are indicated in gray, and those not investigated in this study are indicated in white.