P. Barboro et al., CHANGES IN THE CYTOSKELETAL AND NUCLEAR MATRIX PROTEINS IN RAT HEPATOCYTE NEOPLASTIC NODULES IN THEIR RELATION TO THE PROCESS OF TRANSFORMATION, Experimental cell research, 225(2), 1996, pp. 315-327
In a previous paper (Barboro ct at., 1993, Biophys. J. 65, 1690-1699)
we have shown that cancer development in the resistant hepatocyte mode
l of Solt and Farber is characterized by the progressive unfolding of
the higher-order structure of chromatin. A possible functional role of
decondensation phenomena in cell transformation cannot be ruled out.
Genetic activation involves the relaxation of the superstructure of ch
romatin, which may be, at least in part, modulated by its interaction
with the nuclear matrix. Moreover, recent observations suggest that ge
ne expression can be stimulated by alterations in the organization of
the cytoskeleton. Therefore, we have characterized the changes in comp
osition that the nuclear matrix-intermediate filament complex undergoe
s during the evolution of rat hepatocyte nodules. Dramatic changes in
the expression of both the nuclear matrix and intermediate filament pr
oteins occur during transformation; they are, however, related in a di
fferent way to the stages of carcinogenesis. Several new nuclear matri
x proteins appear in early nodules, isolated 9 weeks after initiation.
The subsequent evolution of persistent nodules is also characterized
by discrete changes in the composition. Thus, the new synthesis of nuc
lear matrix proteins reflects the emergence of successive cellular pop
ulations, in line with the recent finding that a subset of components
of the nuclear matrix is cell type-specific. In contrast, intermediate
filament proteins undergo continuing changes. A new keratin with appa
rent molecular weight of 39 kDa, analogous to human keratin 19, appear
s in early nodules, and its expression steadily increases up to the 32
nd week from initiation; at the same time, the amount of the proteolyt
ic fragments of keratins A and D increases sharply. These findings sug
gest that the inappropriate expression of keratin 19 may be involved i
n the epigenetic activation of new cellular programs, through the rear
rangement of the cytoskeleton which in turn may perturb nuclear matrix
function. (C) 1996 Academic Press, Inc.