RGD Reference Report - Gene-specific inhibition of breast carcinoma in BALB-neuT mice by active immunization with rat Neu or human ErbB receptors. - Rat Genome Database

Send us a Message



Submit Data |  Help |  Video Tutorials |  News |  Publications |  Download |  REST API |  Citing RGD |  Contact   

Gene-specific inhibition of breast carcinoma in BALB-neuT mice by active immunization with rat Neu or human ErbB receptors.

Authors: Masuelli, L  Focaccetti, C  Cereda, V  Lista, F  Vitolo, D  Trono, P  Gallo, P  Amici, A  Monaci, P  Mattei, M  Modesti, M  Forni, G  Kraus, MH  Muraro, R  Modesti, A  Bei, R 
Citation: Masuelli L, etal., Int J Oncol. 2007 Feb;30(2):381-92.
RGD ID: 2289979
Pubmed: PMID:17203220   (View Abstract at PubMed)

Employing the transgenic BALB-neuT mouse tumor model, we explored the in vivo biologic relevance of immunocompetent epitopes shared among the four ErbB receptors. The outcome of neu-mediated tumorigenesis was compared following vaccination with isogeneic normal rat ErbB2/Neu (LTR-Neu) or xenogeneic human ErbB receptors (LTR-EGFR, LTR-ErbB2, LTR-ErbB3 and LTR-ErbB4), each recombinantly expressed in an NIH3T3 murine cell background. Vaccination using rat LTR-Neu at the stage of atypical hyperplasia potently inhibited neu-mediated mammary tumorigenesis. Moreover, all human ErbB receptors specifically interfered with tumor development in BALB-neuT mice. Relative increase in tumor-free survival and reduction in tumor incidence corresponded to structural similarity shared with the etiologic neu oncogene, as rat orthologue LTR-Neu proved most effective followed by the human homologue LTR-ErbB2 and the other three human ErbB receptors. Vaccination resulted in high titer specific serum antibodies, whose tumor-inhibitory effect correlated with cross-reactivity to purified rat Neu extracellular domain in vitro. Furthermore, a T cell response specific for peptide epitopes of rat Neu was elicited in spleen cells of mice immunized with LTR-Neu and was remotely detectable for discrete peptides upon vaccination with LTR-ErbB2 and LTR-EGFR. The most pronounced tumor inhibition by LTR-Neu vaccination was associated with leukocyte infiltrate and tumor necrosis in vivo, while immune sera specifically induced cytotoxicity and apoptosis of BALB-neuT tumor cells in vitro. Our findings indicated that targeted inhibition of neu oncogene-mediated mammary carcinogenesis is conditional upon the immunization schedule and discrete immunogenic epitopes shared to a variable extent by different ErbB receptors.

RGD Manual Disease Annotations    Click to see Annotation Detail View

Objects Annotated

Genes (Rattus norvegicus)
Egfr  (epidermal growth factor receptor)
Erbb2  (erb-b2 receptor tyrosine kinase 2)
Erbb3  (erb-b2 receptor tyrosine kinase 3)
Erbb4  (erb-b2 receptor tyrosine kinase 4)

Genes (Mus musculus)
Egfr  (epidermal growth factor receptor)
Erbb2  (erb-b2 receptor tyrosine kinase 2)
Erbb3  (erb-b2 receptor tyrosine kinase 3)
Erbb4  (erb-b2 receptor tyrosine kinase 4)

Genes (Homo sapiens)
EGFR  (epidermal growth factor receptor)
ERBB2  (erb-b2 receptor tyrosine kinase 2)
ERBB3  (erb-b2 receptor tyrosine kinase 3)
ERBB4  (erb-b2 receptor tyrosine kinase 4)


Additional Information