The Role of Nuclear Matrix Proteins Binding to Matrix Attachment Regions (MARs) in Prostate Cancer Cell Differentiation

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 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.

Over-expression of the special AT rich sequence binding protein 1 (SATB1) promotes the progression of nasopharyngeal carcinoma: association with EBV LMP-1 expression

“…These results indicate that the expression of SATB1 is inversely correlated to NPC cell differentiation. Our findings support the very recent report of Barboro et al, demonstrating that SATB1, a DNA matrix attachment regions (MARs) binding protein, is involved in the differentiation of prostate cancer cells [33]. In the present study, SATB1 expression co-localized with PCNA, a marker of cell proliferation, in NPC cells (Figure  3).…”

A novel role of lamins from genetic disease to cancer biomarkers

“…As the lamins have been identified as a primary component of Nuclear matrix (NM) and Matrix Associated Regions (MARs) the authors speculate that modifying the interactions between NM and MARs may affect gene expression giving rise to a more malignant phenotype. 29 These results are supported by an independent study by a different group which reported that knock-down of a nuclear protein MeCP2 in PC3 and LNCaP cells causes aberrant proliferation and defective cell cycle progression. This defect is accompanied by diminished lamin A/C, lamin B1 and lamin B receptor (LBR) protein levels and altered nuclear shape.…”

High PARP-1 expression is associated with tumor invasion and poor prognosis in gastric cancer

“…This result is concordant with the previously demonstrated inverse correlation between the degree of cell differentiation and PARP-1 activity (37). Barboro et al (38) demonstrated that higher PARP expression levels were detected in a less-differentiated PC3 cell line, as compared with a more-differentiated LNCaP prostate carcinoma cell line. It is possible that PARP-1 upregulation is involved in maintaining the stemness of cells, therefore exhibiting an association with lower differentiation in certain cancer cells.…”