Prevention of HER-2/neu transgenic mammary carcinoma by tamoxifen plus interleukin 12

Patrizia Nanni, Giordano Nicoletti, Carla De Giovanni, Lorena Landuzzi, Emma Di Carlo, Manuela Iezzi, Cinzia Ricci, Annalisa Astolfi, Stefania Croci, Francesco Marangoni, Piero Musiani, Guido Forni, Pier Luigi Lollini

Research output: Contribution to journalArticlepeer-review

Abstract

FVB-NeuN (N#202) female mice transgenic for the HER-2/neu protooncogene driven by the murine mammary tumor virus (MMTV) promoter develop mammary carcinomas with a progression from focal atypical hyperplasia to in situ carcinoma and to invasive carcinoma that closely resembles that of human neoplasia. Here we report that the combination of tamoxifen plus interleukin 12 (IL-12) results in a very effective prevention of mammary carcinogenesis, significantly higher than those obtained with either tamoxifen or IL-12 alone. At I year of age, 20% of control mice resulted tumor-free, whereas 80% of mice receiving the combined treatment were tumor-free. At 2 years of age, less than 5% of control mice were tumor-free, as opposed to 70% of mice treated with tamoxifen plus IL-12. The combined treatment inhibited mammary carcinogenesis mainly through a reduction in the number of mammary cells at risk of progression, a reduction in estrogen receptors (ERs) expression and a reduction in the angiogenic support to mammary development, likely due to cross-talk between tamoxifen and interferony (IFNy) (the main downstream mediator elicited in vivo by IL-12). The addition of IL-12 to the tamoxifen treatment more than doubled mouse lifetime and did not exacerbate known side effects of tamoxifen.

Original languageEnglish
Pages (from-to)384-389
Number of pages6
JournalInternational Journal of Cancer
Volume105
Issue number3
DOIs
Publication statusPublished - Jun 20 2003

Keywords

  • Chemoimmunoprevention
  • HER-2/neu
  • Interleukin 12
  • Mammary carcinoma
  • Tamoxifen

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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