Reference SummaryBoggio K, J Exp Med 1998 Aug 3;188(3):589-96

Title

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

Authors

 Boggio K; Nicoletti G; Di Carlo E; Cavallo F; Landuzzi L; Melani C; Giovarelli M; Rossi I; Nanni P; De Giovanni C; Bouchard P; Wolf S; Modesti A; Musiani P; Lollini PL; Colombo MP; Forni G

Journal

 J Exp Med

Volume

 188

Issue

 3

Year

 1998

Pages

 589-96

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.

Links

 J:49500 – MGI References
9687535 – National Library of Medicine/PubMed

Strain Notes

Strain Note
C.Cg-Tg(MMTV-Erbb2)1Pv Mice carrying this transgene were originally generated on a (B6DF1 x CD-1)F1 genetic background. They were then backcrossed to outbred CD-1. Male mouse no. 1330 had been fully backcrossed to CD-1 and was then backcrossed to BALB/c females for 12 or more generations.
FVB/N-Tg(MMTVneu)202Mul Mice provided by Dr. W.J. Muller.

Models
Strain Model Name Treatment Agent(s) Organ Affected Frequency Model Details
C.Cg-Tg(MMTV-Erbb2)1Pv Mammary gland carcinoma Mammary gland

100
C.Cg-Tg(MMTV-Erbb2)1Pv Mammary gland carcinoma
  • interleukin 12 (IL-12)
 Mammary gland

100
C.Cg-Tg(MMTV-Erbb2)1Pv Mammary gland carcinoma
  • thymectomy
  • anti-CD8+ monoclonal antibody
 Mammary gland

100
C.Cg-Tg(MMTV-Erbb2)1Pv Mammary gland carcinoma
  • thymectomy
  • interleukin 12 (IL-12)
  • anti-CD8+ monoclonal antibody
 Mammary gland

100
FVB/N-Tg(MMTVneu)202Mul Mammary gland carcinoma Mammary gland

100
FVB/N-Tg(MMTVneu)202Mul Mammary gland carcinoma
  • interleukin 12 (IL-12)
 Mammary gland

50
C.Cg-Tg(MMTV-Erbb2)1Pv Mammary gland carcinoma in situ Mammary gland

observed
C.Cg-Tg(MMTV-Erbb2)1Pv Mammary gland carcinoma in situ
  • interleukin 12 (IL-12)
 Mammary gland

0 - observed
FVB/N-Tg(MMTVneu)202Mul Mammary gland carcinoma in situ Mammary gland

observed
C.Cg-Tg(MMTV-Erbb2)1Pv Mammary gland hyperplasia - atypical Mammary gland

observed
C.Cg-Tg(MMTV-Erbb2)1Pv Mammary gland hyperplasia - atypical
  • interleukin 12 (IL-12)
 Mammary gland

observed
FVB/N-Tg(MMTVneu)202Mul Mammary gland hyperplasia - atypical Mammary gland

0