CHANGES IN THE CYTOSKELETAL AND NUCLEAR MATRIX PROTEINS IN RAT HEPATOCYTE NEOPLASTIC NODULES IN THEIR RELATION TO THE PROCESS OF TRANSFORMATION

Citation
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
Citations number
70
Categorie Soggetti
Oncology,"Cell Biology
Journal title
ISSN journal
00144827
Volume
225
Issue
2
Year of publication
1996
Pages
315 - 327
Database
ISI
SICI code
0014-4827(1996)225:2<315:CITCAN>2.0.ZU;2-O
Abstract
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.