© 1997 by Oxford University Press
Journal Of The National Cancer Institute, Vol 89, 1524-1529, Copyright © 1997 by Oxford University Press
B Liu, D Sun, W Xia, MC Hung and D Yu
BACKGROUND: Increased expression of the multidrug resistance gene (MDR-
1)-encoded P-glycoprotein (p170[mdr-1]) is a major cause of tumor cell
multidrug resistance. p170(mdr-1) functions as a drug-efflux pump to reduce
the cellular accumulation of specific drugs. MDA-MB-435 human breast cancer
cells that have been transfected with oncogene c-erbB2 complementary DNA
(435.eb cells) express high levels of the transmembrane glycoprotein
p185(c-erbB2) and exhibit increased resistance to the chemotherapeutic
agent paclitaxel via p170(mdr-1)- independent mechanisms. We have recently
discovered that the widely used monoclonal antibody C219, which is specific
for p170(mdr-1), may cross-react with p185(c-erbB2) in 435.eb cells. In
this study, we have investigated the nature of this cross-reactivity.
METHODS: Immunoprecipitation experiments involving the use of breast cancer
cells that express different levels of p185(c-erbB2) were performed, and
C219 was used for western blot analysis of immunoprecipitated proteins.
Immunohistochemical analyses were performed on acetone-fixed slides of
human breast cancer cells. Peptide sequence comparisons and enzyme-linked
immunosorbent assays were performed to determine the molecular basis of
C219 cross-reactivity with p185(c-erbB2). RESULTS: The cross-reactivity of
C219 with p185(c-erbB2) was demonstrated by both western blot and
immunohistochemical analyses. Peptide sequence comparisons revealed that
C219 recognizes an epitope in p170(mdr-1) (C219 epitope) that shares
sequence homology with p185(c-erbB2). Enzyme- linked immunosorbent assays
demonstrated that C219 recognizes synthetic peptides derived from both the
C219 epitope in p170(mdr-1) and the C219 epitope-homologous region in
p185(c-erbB2). CONCLUSIONS: The anti- p170(mdr-1) monoclonal antibody C219
cross-reacts with p185(c-erbB2) through a peptide sequence in p185(c-erbB2)
that is homologous to the C219 epitope in p170(mdr-1).
ARTICLES
Cross-reactivity of C219 anti-p170(mdr-1) antibody with p185(c-erbB2) in breast cancer cells: cautions on evaluating p170(mdr-1)
Department of Surgical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston 77030, USA.
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