Gene expression analysis of immune-mediated arrest of tumorigenesis in a transgenic mouse model of HER-2/neu-positive basal-like mammary carcinoma.
We previously showed that a vaccine combining interleukin 12 and allogeneic p185(neu)-positive mammary carcinoma cells completely prevented multifocal mammary carcinogenesis in 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, gamma-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.
Astolfi
Annalisa
A
Department of Experimental Pathology, Cancer Research Section, University of Bologna, viale Filopanti 22, I-40126 Bologna, Italy.
Landuzzi
Lorena
L
Nicoletti
Giordano
G
De Giovanni
Carla
C
Croci
Stefania
S
Palladini
Arianna
A
Ferrini
Silvano
S
Iezzi
Manuela
M
Musiani
Piero
P
Cavallo
Federica
F
Forni
Guido
G
Nanni
Patrizia
P
Lollini
Pier-Luigi
PL
D000818:Animals; D019496:Cancer Vaccines / Q000627:therapeutic use*; D004195:Disease Models, Animal; D015870:Gene Expression / Q000187:drug effects; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D008297:Male; D008325:Mammary Neoplasms, Experimental / Q000235:genetics* / Q000276:immunology / Q000517:prevention & control*; D051379:Mice; D008822:Mice, Transgenic; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*
D019496:Cancer Vaccines; D018719:Erb-b2 Receptor Tyrosine Kinases