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  • Title: Altered profiles in nuclear matrix proteins associated with DNA in situ during progression of breast cancer cells.
    Author: Spencer VA, Samuel SK, Davie JR.
    Journal: Cancer Res; 2001 Feb 15; 61(4):1362-6. PubMed ID: 11245435.
    Abstract:
    Nuclear matrix proteins (NMPs) show promise as informative biomarkers in following the pathogenesis of breast cancer. The nuclear matrix is a dynamic RNA-protein network involved in the organization and expression of chromatin. Cisplatin, which preferentially cross-links nuclear matrix proteins to DNA in situ, may be used to identify NMPs that organize and/or regulate the processing of DNA. In this study, we analyzed the nuclear matrix proteins from an estrogen receptor-positive breast cancer cell line panel consisting of MCF-7, MIII, LCC1, and LCC2 cell lines. This cell line panel reflects the stages of malignant progression in breast cancer. Proteins isolated from nuclear matrices and proteins cross-linked to nuclear DNA in situ with cisplatin were analyzed by two-dimensional gel electrophoresis. Specific changes in nuclear matrix proteins bound to nuclear DNA were identified. In concordance with estrogen independence and antiestrogen insensitivity, a loss in cisplatin cross-linking of specific NMPs to nuclear DNA was observed. Our results suggest that progression of breast cancer is accompanied by a reorganization of chromosomal domains, which may lead to alterations in gene expression.
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