Reference SummaryLi B, Oncogene 1998 Feb 26;16(8):997-1007

Title

 A transgenic mouse model for mammary carcinogenesis.

Authors

 Li B; Murphy KL; Laucirica R; Kittrell F; Medina D; Rosen JM

Journal

 Oncogene

Volume

 16

Issue

 8

Year

 1998

Pages

 997-1007

Abstract

 Missense mutations in the p53 tumor suppressor occur frequently in human breast cancer and influence both the prognosis and response to chemotherapy, Amino acid 175 (equivalent to murine 172) is the second most common site of missense mutations in p53 in human breast cancer, Over 95% of these mutations are arginine-to-histidine (R-H) substitutions resulting in a gain-of-function, and not merely a dominant-negative phenotype, Transgenic mice expressing a p53 172(R-H) construct targeted to the mammary gland by means of a whey acidic protein (WAP) promoter were characterized as a model system in order to determine the specific effects of this mutation on mammary tumorigenesis. Although transgene expression alone had no apparent effect on normal mammary development, transgenic mice treated with the chemical carcinogen dimethylbenz(a)anthracene developed tumors with much shorter latency than did control littermates and had a greater tumor burden, Tumors arising in transgenic mice did not exhibit either decreased apoptosis or increased cell proliferation relative to tumors arising in nontransgenic littermates, but did display increased genomic instability, Large pleiomorphic nuclei were visible in many tumors from transgenic mice, and DNA flow analysis confirmed the presence of significant aneuploid cell populations, Since these transgenic mice develop very few spontaneous tumors, while accelerating carcinogen-and oncogene-mediated tumorigenesis, this mouse model will, therefore, be useful in the investigation of early events in mammary tumorigenesis, It may also be used as a preclinical model to test newly developed chemotherapeutic strategies.

Links

 J:46426 – MGI References
9519874 – National Library of Medicine/PubMed

Strain Notes

Strain Note
FVB/N Expression of the wild type allele of the Trp53 gene was reported to not be detected in the mammary glands of these mice during lactation.
The wild type alleles of the Cdkn1a, Pcna, Wap, and Mdm2 genes were reported to be slightly expressed in the mammary glands of these mice during lactation.
FVB/N-Tg(Trp53R172H)8512Jmr The "Trp53R172H" transgene was reported to be highly expressed in the mammary glands of these mice during lactation.
The wild type alleles of the Pcna and Wap genes were reported to be highly expressed, the wild type allele of the Mdm2 gene was reported to be expressed, and the wild type allele of the Cdkn1a gene was reported to be slightly expressed in the mammary glands of these mice during lactation.

Models
Strain Model Name Treatment Agent(s) Organ Affected Frequency Model Details
FVB/N Mammary gland adenoacanthoma
  • pituitary isograft
  • 7,12-dimethylbenz[a]anthracene (DMBA)
 Mammary gland

observed
FVB/N Mammary gland adenocarcinoma
  • pituitary isograft
  • 7,12-dimethylbenz[a]anthracene (DMBA)
 Mammary gland

observed
FVB/N-Tg(Trp53R172H)8512Jmr Mammary gland adenocarcinoma - type B
  • pituitary isograft
  • 7,12-dimethylbenz[a]anthracene (DMBA)
 Mammary gland

observed
FVB/N-Tg(Trp53R172H)8512Jmr Mammary gland adenoma
  • pituitary isograft
  • 7,12-dimethylbenz[a]anthracene (DMBA)
 Mammary gland

observed
FVB/N Mammary gland metaplasia - squamous
  • pituitary isograft
  • 7,12-dimethylbenz[a]anthracene (DMBA)
 Mammary gland

observed
FVB/N-Tg(Trp53R172H)8512Jmr Mammary gland tumor Mammary gland

0 - observed
FVB/N-Tg(Trp53R172H)8512Jmr Mammary gland tumor
  • pituitary isograft
  • 7,12-dimethylbenz[a]anthracene (DMBA)
 Mammary gland

100
FVB/N Mammary gland tumor
  • pituitary isograft
  • 7,12-dimethylbenz[a]anthracene (DMBA)
 Mammary gland

77.0 - 85.0