PMID: 18728395Aug 30, 2008Paper

Mouse models for BRCA1 associated tumorigenesis: from fundamental insights to preclinical utility

Cell Cycle
Peter Bouwman, Jos Jonkers

Abstract

Germline mutations in BRCA1 result in a significant predisposition for breast and ovarian cancer, with frequent LOH of the remaining wild type allele. Soon after the identification of BRCA1, several different knockout mice were generated to study its biological function in vivo. BRCA1, which is involved in DNA double-strand break (DSB) repair, appeared to be essential for embryonic proliferation and survival during mid-gestation. In contrast to human mutation carriers however, heterozygous mouse mutants did not show spontaneous cancer development. Therefore, a number of conditional mouse models were developed. while tumors of these mice show varying degrees of similarity with their human counterparts, two mouse models develop mammary tumors that lack expression of estrogen and progesterone receptors and ERBB2. This 'triple negative' signature is a characteristic feature of BRCA1-associated breast cancers, which can therefore not be treated with endocrine agents or ERBB2-targeting therapeutics. Promising drugs for treating BRCA1-mutated tumors include platinum compounds and PARP inhibitors, which are specifically toxic to DSB repair deficient cells. Although encouraging results have been reported, recent findings indicate that B...Continue Reading

Citations

Oct 12, 2011·Proceedings of the National Academy of Sciences of the United States of America·Hiroyuki KonishiBen Ho Park
Sep 22, 2011·Cancer Prevention Research·Eun-Hee KimKaren T Liby
Jan 7, 2010·BMC Genomics·Michael BoettcherJörg D Hoheisel
Jun 20, 2013·Scientific Reports·Yuichiro SaitoToshiaki Isobe
Mar 31, 2011·Proteomics. Clinical Applications·Regine M SchoenherrAmanda G Paulovich
Apr 22, 2014·DNA Repair·Tomas AparicioJean Gautier
Jan 5, 2011·Protein & Cell·Jiaxue WuXiaochun Yu
Nov 7, 2016·Cold Spring Harbor Symposia on Quantitative Biology·Stefano AnnunziatoJos Jonkers

❮ Previous
Next ❯

Related Concepts

Related Feeds

Breast Cancer: BRCA1 & BRCA2

Mutations involving BRCA1, found on chromosome 17, and BRCA2, found on chromosome 13, increase the risk for specific cancers, such as breast cancer. Discover the last research on breast cancer BRCA1 and BRCA2 here.