A Critique of Pure (Genetic) Information

Dialectics of Disorder: Normalization and Pathology as Process 177
(Kinzler & Vogelstein 1996). What then is it that the APC mutations can
be said to cause?
The sequence of the APC gene does not provide any clues by way of
analogy as to the function of the APC protein because it does not show
homology with other genes or proteins that have been characterized.
Where inferences with respect to APC function are to be found is with
respect to the binding of the APC protein to other proteins. The central
third of APC contains two classes of binding sites for the protein bcatenin.
The catenins are cytoplasmic proteins that bind to the family of
cell-adhesion molecules known as cadherins. Evidence suggests that
binding to b-catenin is necessary for the cadherin to function in binding
adjacent cells together. Given that the binding of b-catenin to cadherin
or to APC is mutually exclusive (i.e., competetive) (Kemler 1993), APC
may function to modulate the ability of the colorectal cells to bind to
adjacent cells. In addition, the binding state of b-catenin will also affect
the transmission of extracellular signals through the plasma membrane
and into the interior of the cell (a process known as signal transduction).
What can best be surmised about APC is as follows. In the absence
of either of the normal alleles a protein is produced which results in
the destabilization of cell-cell interactions in the colorectal epithelium,
giving rise to an altered micromorphology known as polyps. The fact
that these arise only in colorectal tissue, despite the ubiquitous expression
of APC, suggests that it is only in the context of the specific
biochemical-organizational state of differentiated colorectal tissue that
this sensitivity to the status of the APC molecule can be found. The formation
of polyps is a shift in the micro-organizational field of the colorectal
tissue in response to a perturbation. In this case the perturbation
is a change in cell-cell structure due to the alteration of an internal component
which is involved in the architecture of cell-cell adhesion and
signal transmission. Yet by analogy to the example of liver nodules discussed
above, the colorectal polyps may also be a kind of adaptive
response to any agent which presents a challenge to local tissue organization,
whether this agent is internal and inherent or external in origin.
And as in the case of the liver nodules, the colorectal polyps are not
themselves cancerous but are just more prone to becoming so than
normal tissue.