DESCRIPTION (Applicant's Description) Evidence for biological synergism of
plasma-membrane tyrosine kinase receptors erbB-3 and erbB-2 in model systems
and human breast tumor cell lines raises the possibility that coexpression
of these receptors may play a role in tumorigenesis and cell proliferation.
Thus, identifying coexpressing erbB-2 and erbB-3 receptors in tumor
specimens will provide greater specificity, and might identify a
subpopulation of patients with different outcome and chemotherapeutic
potential. However, the existing clinical studies are weak, and the data on
expression of erbB-3 in breast tumors are inconsistent. In particular, the
disagreement among studies with regard to cytoplasmic versus membrane
staining is troubling. A major contributing factor is the poorly
characterized antibody used in all studies.
The goal of this proposal is to validate reagents for detection of erbB-3
expression by immunohistochemistry in paraffin sections of breast tumors.
Therefore, our specific aims are: (1) to perform immunostaining of erbB-3
in transfected and tumor cell lines using five different erbB-3 antibodies,
(2) to localize the cell fraction in which erbB-3 resides in these cell
lines, and (3) to compare the pattern of staining of those antibodies in
tumor specimens.
Using this knowledge, we can establish a valid protocol for quantitating
erbB-3 in breast cancer an evaluating its etiologic prognostic significance.
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