the role of nuclear matrix proteins binding to matrix attachment regions (mars) in prostate cancer cell differentiation核基质蛋白的角色绑定到矩阵附件区域(火星)在前列腺癌的细胞分化.pdfVIP

The Role of Nuclear Matrix Proteins Binding to Matrix Attachment Regions (MARs) in Prostate Cancer Cell Differentiation 1 1 2 1 Paola Barboro , Erica Repaci , Cristina D’Arrigo , Cecilia Balbi * 1 IRCCS Azienda Ospedaliera Universitaria San Martino IST-Istituto Nazionale per la Ricerca sul Cancro, Department of Diagnostic Technologies, Genoa, Italy, 2 C.N.R., Istituto per lo Studio delle Macromolecole, ISMAC, Sezione di Genova, Genoa, Italy Abstract 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