Biology Reference
In-Depth Information
forward a theory in which cancer is not caused by mutations but by
disturbances arising in tissue organisation and not at molecular level
(Sonnenschein and Soto, 1999). This theory seems to be supported
by tissue graft experiments demonstrating that N-nitrosomethylurea
does not induce mutations in the cancerous tissue itself to exert its
carcinogenic effect. In these experiments, the carcinogenesis mecha-
nism seems to work through deregulation in the tissue adjacent
to the cancerous tissue and not through the direct action of muta-
tion in its cells (Maffini
et al
., 2004). Mina Bissell and her team have
likewise demonstrated that cancerous cells can become normal again
when they are treated by signalling pathway inhibitors (Kenny and
Bissell, 2003). These data put the role of mutation into perspective
and show that the cancerous transformation of a cell depends on
its environment (van Kempen
et al
., 2003; Bissell
et al
., 1999).
They can be integrated into the Darwinian model because it stipu-
lates that tissue organisation depends on the microenvironmental
selective constraint that it exerts on the cells. The model can even
remove inconsistencies between experimental data which are at first
sight contradictory.
Indeed, while the role of the microenvironment in cancerisation
is now a well-established fact, the role of mutation is equally undis-
putable. How can the two be reconciled? Jean-Pascal Capp has
made an interesting analysis of this subject. We have already indi-
cated that according to our model mutation could be involved in
destroying overall tissue equilibrium, but this equilibrium could
also be disrupted due to disturbances in the microenvironment. In
both cases, the cells would be subject to gene expression deregula-
tion since this expression is controlled by the microenvironment.
Deregulation could then affect the genes, which are known to con-
trol rates of mutation, and cause an increase in the latter in the
cells. In turn, through their effects these mutations would con-
tribute to extending cell cancerisation. In this context, mutation is
not therefore the obligatory initial cause of cancer but an effect of
the imbalance between the influence of the microenvironment and
the stochastic expression of genes. It is an aggravating factor in the
process of cancerisation (Capp, 2005, in press).
