Journal Papers Modeling time-dependent transcription effects of HER2 oncogene and discovery of a role for E2F2 in breast cancer cell-matrix adhesion


Our method highlighted regulatory interactions previously identified in the cell line and a novel finding that the HER2 oncogene, as opposed to the proto-oncogene, upregulates expression of the E2F2 transcription factor. By targeted gene knockdown we show the significance of this, demonstrating that cancer cell-matrix adhesion and outgrowth were markedly inhibited when E2F2 levels were reduced. Thus, validating in this context that upregulation of E2F2 represents a key intermediate event in a HER2 oncogene-directed gene expression-based signaling circuit. This work demonstrates how predictive modeling of longitudinal gene expression data combined with multiple systems-level analyses can be used to accurately predict downstream signaling pathways. Here, our integrated method was applied to reveal insights as to how the HER2 oncogene drives a specific cancer cell phenotype, but it is adaptable to investigate other oncogenes and model systems.

Paper Details


A. Bollig-Fischer,  L. Marchetti,  C. Mitrea,  J. Wu,  A. Kruger,  V. Manca,  S. Draghici


Bioinformatics, 30, , 3036-43