Role of the Wnt-4 Protein in the Mouse Mammary Gland
Abstract
Germilne mutations in BRCA1 are the most common cause of familial breast cancer. In addition to full length BRCA1, both human and mouse cells express an alternatively spliced variant, BRCA1-DELTA 11 that lacks exon 11 in its entirety. The finding that murine embryos bearing homozygous deletions of exon 11 of Brca1 survive longer than embryos that are homozygous for null alleles suggests that exon 11-deleted isoforms may perform at least some of the functions of Brca1. To resolve this apparent inconsistency, and to address the functions of exon 11-deleted isoforms of Brca1, we have analyzed the Brca1 protein in cells derived from a murine model in which only the exon 11-deleted Brca1 isoform is expressed. Our results demonstrate that mouse Brca1 is identical to human BRCA1 with respect to its cell cycle regulation, DNA damage-induced phosphorylation, nuclear localization, and association with Rad51. We show that endogenous exon 11-deleted isoforms of Brca1 localize to discrete nuclear foci indistinguishable from those found in wild type cells, despite the fact that they lack previously defined nuclear localization signals encoded in exon 11. We show that exon 11-deleted Brca1 is not phosphorylated in response to DNA damage, unlike full length Brca1, and that gamma-irradiation-induced Rad51 foci formation is significantly reduced in cells expressing only the exon 11-deleted isoform.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2001
- Accession Number
- ADA405345
Entities
People
- Lewis A Chodosh
- Louise J. Huber
Organizations
- University of Pennsylvania