Carcinogenesis, Vol. 22, No. 2, 343-346,
February 2001
© 2001 Oxford University Press
SHORT COMMUNICATION |
Heterozygosity for a mutation in Brca1 or Atm does not increase susceptibility to ENU-induced mammary tumors in ApcMin/+ mice
1 Laboratory of Genetics and
2 Department of Human Oncology, University of Wisconsin-Madison, Madison, WI 53792,
3 Genetic Disease Research Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD and
4 Departments of Pediatrics and Medicine, University of California, San Diego School of Medicine, San Diego, CA, USA
The proteins encoded by BRCA1 and ATM may be important in DNA repair and maintenance of genomic integrity. Women heterozygous for a mutation in BRCA1 have an increased incidence of breast cancer. Some evidence also suggests that female carriers of ATM mutations may be susceptible to breast cancer. However, mice carrying one mutant allele of Brca1 or Atm are not highly susceptible to breast cancer. We proposed that heterozygosity for a mutant allele of Brca1 or Atm may confer a decreased ability to repair DNA damage. Such a defect might lead to a heightened sensitivity to tumor development in susceptible animal models. Therefore, mice predispose to mammary tumor development might show an increased susceptibility if they also carry an Atm or Brca1 mutation. C57BL/6J (B6) Min/+ mice are predisposed to mammary and intestinal tumors and exposure to the point mutagen ethylnitrosourea (ENU) markedly increases mammary tumor multiplicity and incidence. To test our hypothesis, B6.Min/+ male mice were crossed with 129S6/SvEvTac females heterozygous for a mutant allele of either Brca1 or Atm. Female progeny from each cross were treated with ENU and followed for tumor development. Only Min/+ F1 females developed mammary tumors and heterozygosity for a mutant Brca1 or Atm allele had no effect on mammary or intestinal tumor incidence and multiplicity. These results suggest that heterozygosity for a mutation in Brca1 or Atm does not affect Min-induced tumorigenesis in mice under these conditions. Additionally, exposure to a somatic point mutagen does not increase tumor development in mice carrying Brca1 or Atm mutations.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  S. Lu, K. Shen, Y. Wang, S. J. Santner, J. Chen, S.C. Brooks, and Y.A. Wang Atm-haploinsufficiency enhances susceptibility to carcinogen-induced mammary tumors Carcinogenesis, April 1, 2006; 27(4): 848 - 855. [Abstract] [Full Text] [PDF]
|
|