Reference SummaryDi Carlo E, Lab Invest 1999 Oct;79(10):1261-9

Title

 Analysis of mammary carcinoma onset and progression in HER-2/neu oncogene transgenic mice reveals a lobular origin.

Authors

 Di Carlo E; Diodoro MG; Boggio K; Modesti A; Modesti M; Nanni P; Forni G; Musiani P

Journal

 Lab Invest

Volume

 79

Issue

 10

Year

 1999

Pages

 1261-9

Abstract

 Morphologic examinations of mammary neoplasias arising in BALB/c (H-2d) mice carrying the activated rat HER-2/neu oncogene (BALB-NeuT), and in FVB (H-2q) mice bearing the wild-type proto-oncogene (FVB-NeuN), indicate that both conditions result in a very human-like lobular carcinoma of alveolar type, whose histotype is the result of the preferential expression of HER-2/neu products in the epithelium of lobular ducts and lobules. Detailed analysis of tumor progression indicates that transition from lobular hyperplasia to overt carcinoma is associated with a high epithelial proliferation rate, as assessed by anti-proliferating cell nuclear antigen immunostaining, and coincides with the activation and maximal extension of tumor angiogenic process as assessed by microvessel count (anti-CD31), anti-beta3 integrin, and anti-laminin immunostaining. Neovascularization is accompanied by vascular endothelial cell growth factor and basic fibroblast growth factor production by hyperplastic epithelial cells. By contrast with the BALB-NeuT tumors, E-cadherin expression is almost nonexistent in those arising in FVB-NeuN mice and this may explain their high metastatic potential. Despite their different kinetics, however, the lung metastases observed in both strains are histologically similar and resemble the primary tumor. Both strains can thus be proposed as models for 'in vivo' investigation of the origin and progression of the alveolar type of lobular mammary carcinoma and the testing of new therapeutic approaches.

Links

 J:58098 – MGI References
10532589 – 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
CD-1.Cg-Tg(MMTV-Erbb2)1Pv Mammary gland carcinoma Mammary gland

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

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

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

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

observed