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Mardi 7 juin 2005 à 15 heures
 Version
imprimable
Dr Jean - Jacques KUPIEC
(Ecole Normale Supérieure, Paris)
Modeling embryogenesis and cancer : an approach based on an
equilibrium between the autostabilization of stochastic gene
expression
and the interdependence of cells for proliferation
A large amount of data demonstrating the stochastic nature of
gene expression and cell differentiation has accumulated during the
last 40 years. These data suggest that a gene in a cell always has a
certain probability of being activated at any time and that instead
of leading to on and off switches in an all-or-nothing fashion, the
concentration of transcriptional regulators increases or decreases
this probability. In order to integrate these data in an appropriate
theoretical frame, we have tested the relevance of the selective
model of cell differentiation by computer simulation experiments.
This model is based on stochastic gene expression controlled by
cellular interactions. Our results show that it is readily able to
produce tissue organization. A model involving only two cells
generated a bi-layer cellular structure of finite growth. Cell death
was not a drawback but an advantage because it improved the
viability of this bi-layer structure. However, our results also show
that cellular interactions cannot be simply based on raw selection
between cells. Instead, tissue coordination includes at least two
basic components: phenotypic autostabilization (differentiated cells
stabilize their own phenotype) and interdependence for proliferation
(differentiated cells stimulate the proliferation of alien
phenotypes). In this modified autostabilization-selection model,
cellular organization and growth arrest result from a quantitative
equilibrium between the parameters controlling these two processes.
An imbalance leads to tissue disorganization and invasive
cancer-like growth. These findings suggest that cancer does not
result solely from mutations in the cancerous cell but from the
progressive addition of several small alterations of the equilibrium
between autostabilization and interdependence for proliferation. In
this frame, it is not solely the cancerous cell that is abnormal.
The whole organism is involved. Tumor growth is a local effect of an
imbalance between all the factors involved in tissue organization.
Laforge B, Guez D, Martinez M, Kupiec JJ. Modeling
embryogenesis and cancer: an approach based on an equilibrium
between the autostabilization of stochastic gene expression and
the interdependence of cells for proliferation. Prog Biophys Mol
Biol., 89(1):93-120 (2005)
Contact :
Jean Pascal Capp
SALLE FERNAND GALLAIS, Laboratoire de
Chimie de Coordination
205 route de Narbonne TOULOUSE CEDEX 4 |
