Blocking 53BP1 Expression Lessens Tumor Development in BRCA1-Defective Mice

Fri, 06/18/2010 - 10:00

Our antibody database at Novus Biologicals provides research tools for the forefront of cancer research. Recently, a mouse study using 53BP1 and BRCA1 antibodies showed that deletion of 53BP1 greatly lessened the incidence of tumor development in mice carrying the mutated BRCA1 gene.

The BRCA1 protein is important in the homologous recombination (HR) DNA repair pathway, repairing the replication-associated chromosome breaks which can occur during cell division. If the HR pathway becomes inactive through BRCA1 mutation, the cell relies on alternative repair pathways. However, these are more mutagenic than BRCA1, and can cause formation of abnormal chromosome structures, increasing the risk of cancer. 53BP1 is a binding protein, known to localize to DNA repair sites, in particular double-strand breaks. However, it is not thought to be mutagenic.

A study carried out by Nussenzweig, et al. of the National Cancer Institute of America, set out to look at ways to inhibit tumor formation in a strain of BRCA-1 defective mice, which produce breast tumors similar to those seen in humans. A much lower incidence of tumor development had been noted in mice where 53BP1 was also defective, so in vitro antibody studies were performed. These showed that inactivation of 53BP1 restored HR to Brca1-deficient cells.

Western Blot: 53BP1 Antibody Western Blot: 53BP1 Antibody

A model was suggested whereby, when both BRCA1 and 53BP1 are present at replication breaks, BRCA1 displaces 53BP1 allowing HR to progress unimpeded. In BRCA1-deficient cells, 53BP1 binding at the site disrupts the action of other HR proteins, allowing repair to occur via a mutagenic pathway. When 53BP1 is blocked, HR can occur normally. In other words, deletion of both proteins allows a tumor-free HR pathway. Therefore, if the BRCA1 gene seems to be mutagenic, a possible therapy to prevent tumor growth would be to blcok 53BP1.

With questions also raised over secondary mutations causing resistance to chemotherapy drugs, it is an exciting time for our antibody catalogue.

Novus Biologicals offers many 53BP1 reagents for your research needs including:

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