In
tumor progression definite alterations in nuclear matrix (NM)
protein composition as well as in
chromatin structure occur. The NM interacts with
chromatin via specialized DNA sequences called matrix attachment regions (MARs). In the present study, using a proteomic approach along with a two-dimensional Southwestern assay and confocal
laser microscopy, we show that the differentiation of stabilized human prostate
carcinoma cells is marked out by modifications both NM
protein composition and bond between NM
proteins and MARs. Well-differentiated
androgen-responsive and slowly growing LNCaP cells are characterized by a less complex pattern and by a major number of
proteins binding MAR sequences in comparison to 22Rv1 cells expressing
androgen receptor but
androgen-independent. Finally, in the poorly differentiated and strongly aggressive
androgen-independent PC3 cells the complexity of NM pattern further increases and a minor number of
proteins bind the MARs. Furthermore, in this cell line with respect to LNCaP cells, these changes are synchronous with modifications in both the nuclear distribution of the MAR sequences and in the average loop dimensions that significantly increase. Although the expression of many NM
proteins changes during dedifferentiation, only a very limited group of
MAR-binding proteins seem to play a key role in this process. Variations in the expression of
poly (ADP-ribose) polymerase (PARP) and special AT-rich sequence-binding protein-1 (SATB1) along with an increase in the phosphorylation of
lamin B represent changes that might trigger passage towards a more aggressive phenotype. These results suggest that elucidating the
MAR-binding proteins that are involved in the differentiation of
prostate cancer cells could be an important tool to improve our understanding of this
carcinogenesis process, and they could also be novel targets for
prostate cancer therapy.