Interleukin 12-mediated prevention of spontaneous mammary adenocarcinomas in two lines of HER-2/neu transgenic mice

Katia Boggio, Giordano Nicoletti, Emma Di Carlo, Federica Cavallo, Lorena Landuzzi, Cecilia Melani, Mirella Giovarelli, Ilaria Rossi, Patrizia Nanni, Carla De Giovanni, Page Bouchard, Stanley Wolf, Andrea Modesti, Piero Musiani, Pier Luigi Lollini, Mario P. Colombo, Guido Forni

Research output: Contribution to journalArticlepeer-review

Abstract

The ability of interleukin (IL)-12 to prevent tumors when administered to individuals with a genetic risk of cancer was studied in two lines of transgenic mice expressing rat HER-2/neu oncogene in the mammary gland. Female BALB/c (H-2(d)) mice carrying the activated HER-2/neu oncogene show no morphological abnormalities of the mammary gland until 3 wk of age. They then progress through atypical hyperplasia to in situ lobular carcinoma and at 33 wk of age all 10 mammary glands display invasive carcinomas. Adult FVB mice (H-2(q)) carrying the HER-2/neu protooncogene develop mammary carcinomas with a longer latency (38-49 wk) and a lower multiplicity (mean of 2.6 tumors/mice). Treatment with IL-12 (5 daily intraperitoneal injections, 1 wk on, 3 wk off; the first course with 50 ng IL-12/day, the second with 100 ng IL-12/day) begun at 2 wk of age in BALB/c mice and at 21 wk of age in FVB mice markedly delayed tumor onset and reduced tumor multiplicity. Analogous results were obtained in immunocompetent and permanently CD8+ T lymphocyte- depleted mice. In both transgenic lines, tumor inhibition was associated with mammary infiltration of reactive cells, production of cytokines and inducible nitric oxide synthase, and reduction in microvessel number, in combination with a high degree of hemorrhagic necrosis.

Original languageEnglish
Pages (from-to)589-596
Number of pages8
JournalJournal of Experimental Medicine
Volume188
Issue number3
DOIs
Publication statusPublished - Aug 3 1998

Keywords

  • Adenocarcinomas
  • Angiogenesis
  • Her-2/neu
  • Interleukin 12
  • Tumor prevention

ASJC Scopus subject areas

  • Immunology

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