Convergence of Logic of Cellular Regulation in Different Premalignant Cells by an Information Theoretic Approach

We identify a major transcription pattern that represents a contraction of signaling networks accompanied by induction of cellular proliferation and protein metabolism, which is essential for full transformation. In addition, a more minor, "tumor signature" transcription pattern completes the transformation process. The variation with time of the importance of each transcription pattern is determined. Midway through the transformation, at the stage when cells switch from slow to fast growth rate, the major transcription pattern undergoes a total inversion of its weight while the more minor pattern does not contribute before that stage.A similar network reorganization occurs in two very different cellular transformation models: WI-38 and the cervical cancer HF1 models. Our results suggest that despite differences in a list of transcripts expressed in different cancer models the rationale of the network reorganization remains essentially the same.Deciphering regulatory events that drive malignant transformation represents a major challenge for systems biology. Here, we analyzed the genome-wide transcription profiling of an in vitro cellular system, in which cells were induced to transform to a cancerous phenotype, through intermediate states. Cells evolving towards a malignant state exhibit changes in gene expression that do away with pathways that interfere with proliferation [1]. Cancer cells also appear to be less subject to some of the restrictions and controls characteristic of multicellular organisms [1]. For different cancers many oncogenes and tumor suppressors have been identified [2], but determining a list of genes that characterize cancers has not been fully successful [3].In this study we are using a physically motivated method of gene expression analysis based on the proposition that the process of gene expression is subject to the same quantitative laws as inanimate nonequilibrium systems in physics and chemistry. This allows us to apply a thermodynamic