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Prevention of HER‐2/neu transgenic mammary carcinoma by tamoxifen plus interleukin 12
Author(s) -
Nanni Patrizia,
Nicoletti Giordano,
De Giovanni Carla,
Landuzzi Lorena,
Di Carlo Emma,
Iezzi Manuela,
Ricci Cinzia,
Astolfi Annalisa,
Croci Stefania,
Marangoni Francesco,
Musiani Piero,
Forni Guido,
Lollini PierLuigi
Publication year - 2003
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.11092
Subject(s) - tamoxifen , antiestrogen , mammary gland , mammary tumor , carcinogenesis , cancer research , genetically modified mouse , medicine , tumor progression , endocrinology , transgene , hyperplasia , biology , cancer , breast cancer , biochemistry , gene
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 1 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 interferon‐γ (IFN‐γ) (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. © 2003 Wiley‐Liss, Inc.