Finding a model, finding a cure

May 14, 2001

A major hurdle in the development of an animal model of hereditary breast cancer in humans has been overcome.

Breast cancer is the most prevalent type of cancer in women, with 192,000 new cases expected this year in the US alone. Despite extensive research efforts, scientists have been unable develop a mouse model of hereditary breast cancer. Until now.

As published in the May 15th issue of Genes & Development, a collaboration of researchers from Columbia University and the Dana-Farber Cancer Institute have generated a mouse strain with an inherited mutation in Brca1. The breast and ovarian cancer susceptibility gene, Brca1, is the most commonly detected genetic mutation in familial breast and ovarian cancer. Although structural analysis and in vitro cell culture studies have yielded some clues, the precise function of BRCA1 remains unknown. This work by Dr. Efstratiadis and colleagues represents an enormous advance in the determination of BRCA1 function in tumorigenesis.

Several previous attempts have been made to generate BRCA1-deficient mice. However, these attempts were unsuccessful due to the embryonic death of the mice that had two deficient copies of Brca1, and the fact that mice with only one defective copy of Brca1 did not develop tumors. Dr. Efstratiadis and colleagues modeled their experimental approach after a human breast cancer patient who had inherited homozygous mutations in Brca1 that presumably led to the production of a shortened, or truncated, BRCA1 protein. The scientists generated a mouse strain with a truncating Brca1 mutation that similarly eliminates the C-terminal portion of the BRCA1 protein.

These BRCA1 hypomorphic mice are viable, and they develop a variety of tumors, including breast tumors. As 1 in 9 women will be diagnosed with breast cancer in her lifetime, this work has widespread implications as a therapeutic and research model for hereditary breast cancer.

Cold Spring Harbor Laboratory

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