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Brca1 heterozygous mice have shortened life span and are prone to ovarian tumorigenesis with haploinsufficiency upon ionizing irradiation.

Abstract：

:BRCA1 mutation carriers have an 85% lifetime risk of breast cancer and 60% for ovarian cancer. BRCA1 facilitates DNA double-strand break repair, and dysfunction of BRCA1 leads to hypersensitivity to DNA damaging agents and consequently genomic instability of cells. In this communication, we have examined the tumor incidence and survival of Brca1 heterozygous female mice. Brca1 heterozygotes appear to have a shortened life span with 70% tumor incidence. Lymphoma, but not ovarian and mammary gland tumors, occurs commonly in these mice. After a whole-body exposure to ionizing radiation, Brca1 heterozygous mice have a 3-5-fold higher incidence specific to ovarian tumors, but not lymphoma, when compared with the Brca1+/+ mice. All the tumors from heterozygous mice examined retain the wild-type allele and the cancer cells express Brca1 protein, precluding the chromosomal mechanism for loss of heterozygosity of Brca1 locus. Although the manifestation of BRCA1 haploinsufficiency may be different between human and mouse, this study suggests that women carrying Brca1 mutations may be more prone to ovarian tumor formation after IR exposure than nonmutation carriers.

journal_name

Oncogene

journal_title

Oncogene

authors

Jeng YM,Cai-Ng S,Li A,Furuta S,Chew H,Chen PL,Lee EY,Lee WH

doi

10.1038/sj.onc.1210451

subject

Has Abstract

pub_date

2007-09-13 00:00:00

pages

6160-6

issue

42

eissn

0950-9232

issn

1476-5594

pii

1210451

journal_volume

26

pub_type

杂志文章

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