Functional Analysis of BORIS, a Novel DNA Binding Protein.

摘要

BORIS (CTCFL) is a paralogue of the gene encoding CTCF, a multifunctional DNA binding protein that utilizes different sets of zinc fingers to mediate distinct gene regulatory functions, including those involved in cell growth regulation. Unlike CTCF, the expression of BORIS is normally restricted to specific cells in testes (the only cells where CTCF is not expressed), where it may play a role in reprogramming the methylation pattern of male germ line DNA. To define the possible consequences of aberrant BORIS expression in human breast cancers, we have used a well-characterized human mammary epithelial cell (HMEC) culture model. Our results indicate that in most breast cancer cells, endogenous BORIS is unlikely to be expressed at sufficient levels to interfere with CTCF functions, and that BORIS expression alone is not an efficient immortalizing factor. However, under certain conditions BORIS may cooperate with other changes (e.g. p53 inactivation) to destabilize the genomes of the cells in which it is aberrantly expressed. BORIS expression may cause genomic instability through aberrant affects on centrosome duplication during the cell cycle, and through effects on the regulation of several key early growth response genes.