Gene expression analysis of immune-mediated arrest of tumorigenesis in a transgenic mouse model of HER-2/neu-positive basal-like mammary carcinoma

Annalisa Astolfi, Lorena Landuzzi, Giordano Nicoletti, Carla De Giovanni, Stefania Croci, Arianna Palladini, Silvano Ferrini, Manuela Iezzi, Piero Musiani, Federica Cavallo, Guido Forni, Patrizia Nanni, Pier Luigi Lollini

Research output: Contribution to journalArticlepeer-review

Abstract

We previously showed that a vaccine combining interleukin 12 and allogeneic p185neu-positive mammary carcinoma cells completely prevented multifocal mammary carcinogenesis ih HER-2/neu transgenic mice. To identify the molecular events responsible for effective tumor prevention and to define the tumor gene expression signature, we used microarrays to analyze the expression profile of mammary tissue of untreated transgenic mice and of vaccine-treated, tumor-free mice at different time points. Mammary tissue from vaccinated mice displayed a gene expression profile different from that of untreated, tumor-bearing mice but similar to that of normal/hyperplastic mammary gland. Comparison of treated and untreated-mice at 15 weeks of age revealed up-regulation of genes encoding antibodies, chemokines, γ-interferon- induced genes and inflammatory molecules, and down-regulation of early genes induced by tumor development The gene expression signature of HER-2/neu-transformed tumor cells showed modulation of genes promoting proliferation, angiogenesis, migration, invasion, and metastasis and inhibiting apoptosis and immune response. Meta-analysis of microarray data on human breast cancer showed that the signature of tumors arising in murine HER-2/neu transgenic model correctly classified human HER-2/neu-expressing tumors and normal breast tissue. Moreover murine and human HER-2/neu-positive tumors share the signature of basal-like breast cancers. This gene expression analysis reveals the immune events associated with prevention of tumor development and shows that HER-2/neu transgenic mice represent a good model of a poor-prognosis group of human breast tumors.

Original languageEnglish
Pages (from-to)1205-1216
Number of pages12
JournalAmerican Journal of Pathology
Volume166
Issue number4
Publication statusPublished - Apr 2005

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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