HER-2/neu (neu) transgenic mice (neu-N mice), which express the nontransforming rat proto-oncogene, demonstrate immunological tolerance to neu that is similar to what is encountered in patients with neu-expressing breast cancer. We have shown previously that a significant increase in neu-specific T cells, but no induction of neu-specific antibody, is seen after neu-specific vaccination in neu-N...

Overexpression of the oncogene amplified in breast cancer 1 (AIB1)/steroid receptor coactivator-3 (SRC-3) induces mammary tumorigenesis in mice. In breast cancer, high levels of AIB1/SRC-3 and the growth factor receptor HER2/neu predict resistance to endocrine therapy and poor outcome. However, a mechanistic relationship between AIB1/SRC-3 and HER2/neu in the development of breast cancer has no...

ErbB-2 overexpression and amplification occurs in 15% to 30% of human invasive breast carcinomas associated with poor clinical prognosis. Previously, we have shown that four ErbB-2/Neu tyrosine-autophosphorylation sites within the cytoplasmic tail of the receptor recruit distinct adaptor proteins and are sufficient to mediate transforming signals in vitro. Two of these sites, representing the g...

PURPOSE HER2/neu is frequently overexpressed in breast cancer. In a mouse model, vaccination with HER2/neu DNA elicits antibodies that confer partial protection against tumor challenge. EXPERIMENTAL DESIGN To enhance antitumor immunity, we fused cDNA encoding Flt-3 ligand (FL) to the rat HER2/neu extracellular domain (neu), generating a chimeric FLneu molecule. FLneu and neu DNA vaccines were...

PURPOSE To evaluate HER-2/neu-specific antibody immunity in patients with breast cancer, to determine the rate of occurrence of serum antibodies to HER-2/neu in patients with breast cancer, and to relate the presence of specific immunity to overexpression of HER-2/neu protein in primary tumor. METHODS The antibody response to HER-2/neu protein was analyzed in 107 newly diagnosed breast cancer...

Overexpression of the oncogene amplified in breast cancer 1 (AIB1)/steroid receptor coactivator-3 (SRC-3) induces mammary tumorigenesis in mice. In breast cancer, high levels of AIB1/SRC-3 and the growth factor receptor HER2/neu predict resistance to endocrine therapy and poor outcome. However, a mechanistic relationship between AIB1/SRC-3 and HER2/neu in the development of breast cancer has no...

Prolonged administration of HER-2/neu-specific monoclonal antibody therapy is now widely used for the treatment of HER-2/neu-overexpressing tumors in advanced-stage breast cancer patients. Monoclonal antibody therapy has the potential to promote reduced tumor expression of HER-2/neu by receptor down-modulation and/or the generation of antigen-negative variants. Loss of antigen by either mechani...

Background: The HER-2/neu gene is located on chromosome 17q21 and encodes a 185-kDa transmembrane glycoprotein with tyrosine kinase activity reported to be released in soluble form in various malignancies. Objective: To evaluate the clinical significance of soluble Her-2/neu as a diagnostic marker in lung cancer. Methods: Serum levels of soluble HER-2/neu were measured in 43 patients with lung ...