A transgenic mouse model for mammary carcinogenesis

Baolin Li, Kristen L. Murphy, Rodolfo Laucirica, Frances Kittrell, Daniel Medina, Jeffrey M. Rosen

Research output: Contribution to journalArticle

72 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)997-1007
Number of pages11
JournalOncogene
Volume16
Issue number8
DOIs
StatePublished - Feb 26 1998

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Transgenic Mice
Carcinogenesis
Breast
Neoplasms
Missense Mutation
Carcinogens
Breast Neoplasms
Mutation
Genomic Instability
Aneuploidy
Human Mammary Glands
Tumor Burden
Transgenes
Oncogenes
Histidine
Arginine
Cell Proliferation
Apoptosis
Phenotype
Amino Acids

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Genetics
  • Cancer Research

Cite this

Li, B., Murphy, K. L., Laucirica, R., Kittrell, F., Medina, D., & Rosen, J. M. (1998). A transgenic mouse model for mammary carcinogenesis. Oncogene, 16(8), 997-1007. https://doi.org/10.1038/sj.onc.1201621

A transgenic mouse model for mammary carcinogenesis. / Li, Baolin; Murphy, Kristen L.; Laucirica, Rodolfo; Kittrell, Frances; Medina, Daniel; Rosen, Jeffrey M.

In: Oncogene, Vol. 16, No. 8, 26.02.1998, p. 997-1007.

Research output: Contribution to journalArticle

Li, B, Murphy, KL, Laucirica, R, Kittrell, F, Medina, D & Rosen, JM 1998, 'A transgenic mouse model for mammary carcinogenesis', Oncogene, vol. 16, no. 8, pp. 997-1007. https://doi.org/10.1038/sj.onc.1201621
Li B, Murphy KL, Laucirica R, Kittrell F, Medina D, Rosen JM. A transgenic mouse model for mammary carcinogenesis. Oncogene. 1998 Feb 26;16(8):997-1007. https://doi.org/10.1038/sj.onc.1201621
Li, Baolin ; Murphy, Kristen L. ; Laucirica, Rodolfo ; Kittrell, Frances ; Medina, Daniel ; Rosen, Jeffrey M. / A transgenic mouse model for mammary carcinogenesis. In: Oncogene. 1998 ; Vol. 16, No. 8. pp. 997-1007.
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