Information-theoretic analysis of phenotype changes in early stages of carcinogenesis
Open Access
- 17 May 2010
- journal article
- research article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences of the United States of America
- Vol. 107 (22), 10324-10329
- https://doi.org/10.1073/pnas.1005283107
Abstract
Cancer is a multistep process characterized by altered signal transduction, cell growth, and metabolism. To identify such processes in early carcinogenesis we use an information theoretic approach to characterize gene expression quantified as mRNA levels in primary keratinocytes (K) and human papillomavirus 16 (HPV16)-transformed keratinocytes (HF1 cells) from early (E) and late (L) passages and from benzo(a)pyrene-treated (BP) L cells. Our starting point is that biological signaling processes are subjected to the same quantitative laws as inanimate, nonequilibrium chemical systems. Environmental and genomic constraints thereby limit the maximal thermodynamic entropy that the biological system can reach. The procedure uncovers the changes in gene expression patterns in different networks and defines the significance of each altered network in the establishment of a particular phenotype. The development of transformed HF1 cells is shown to be represented by one major transcription pattern that is important at all times. Two minor transcription patterns are also identified, one that contributes at early times and a distinguishably different pattern that contributes at later times. All three transcription patterns defined by our analysis were validated by gene expression values and biochemical means. The major transcription pattern includes reduced transcripts participating in the apoptotic network and enhanced transcripts participating in cell cycle, glycolysis, and oxidative phosphorylation. The two minor patterns identify genes that are mainly involved in lipid or carbohydrate metabolism.Keywords
This publication has 22 references indexed in Scilit:
- Shift from Apoptotic to Necrotic Cell Death during Human Papillomavirus-induced Transformation of KeratinocytesPublished by Elsevier BV ,2009
- Potential landscape and flux framework of nonequilibrium networks: Robustness, dissipation, and coherence of biochemical oscillationsProceedings of the National Academy of Sciences of the United States of America, 2008
- Microarray analyses of SREBP-1a and SREBP-1c target genes identify new regulatory pathways in musclePhysiological Genomics, 2008
- Optimization of Energy-Consuming Pathways towards Rapid Growth in HPV-Transformed CellsPLOS ONE, 2007
- Genome Expression Pathway Analysis Tool – Analysis and visualization of microarray gene expression data under genomic, proteomic and metabolic contextBMC Bioinformatics, 2007
- Potential Energy Landscape and Robustness of a Gene Regulatory Network: Toggle SwitchPLoS Computational Biology, 2007
- A Specific Role for AKT3 in the Genesis of Ovarian Cancer through Modulation of G2-M Phase TransitionCancer Research, 2006
- Autocrine laminin-5 ligates α6β4 integrin and activates RAC and NFκB to mediate anchorage-independent survival of mammary tumorsThe Journal of cell biology, 2003
- Enhancement of anchorage‐independent growth of human pancreatic carcinoma MIA PaCa‐2 cells by signaling from protein kinase C to mitogen‐activated protein kinaseMolecular Carcinogenesis, 2002
- Information Theory Approach to Molecular Reaction DynamicsAnnual Review of Physical Chemistry, 1978