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Gene/Protein
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Target Concepts:
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Query: UNIPROT:P04626 (
erbB-2
)
5,251
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
We have previously shown that neu oncogene-initiated rat mammary carcinomas uniquely over-express neu-related lipocalin (NRL), a member of the calycin protein superfamily. Here, we characterize the putative human homolog of NRL,
neutrophil gelatinase-associated lipocalin
(
NGAL
). ngal gene expression was found at moderate levels in only 2 of 17 human tissues examined, breast and lung. When breast cancers were examined for
NGAL
mRNA and protein levels, they were found to exhibit heterogeneous expression.
NGAL
levels varied in these tumors from undetectable to exceeding those in normal breast parenchyma. Immuno-histochemical analysis confirmed the presence of
NGAL
within breast carcinoma cells but detected only low levels of this protein in normal ductal epithelium. In contrast, large amounts of the protein were localized to the lumen of normal breast ducts in the vicinity of
NGAL
-expressing tumors. Interestingly, unlike NRL in rat mammary carcinomas, no significant association between
NGAL
expression and
HER-2/neu
activation was found in human breast tumors. In contrast, a significant correlation between
NGAL
expression in breast cancer was found with several other markers of poor prognosis, including estrogen and progesterone receptor-negative status and high proliferation (S-phase fraction).
NGAL
levels were stratified as high or low in breast cancers from a cohort of node-positive patients with known outcome. No significant association between
NGAL
expression and disease-free or overall survival was observed.
...
PMID:Heterogeneous expression of the lipocalin NGAL in primary breast cancers. 984 63
Neutrophil gelatinase-associated lipocalin
(
NGAL
) is a small, secreted glycoprotein with proposed functions in cell proliferation, survival and morphogenesis.
NGAL
is expressed in a variety of tumor types including breast carcinomas, but it is not known whether
NGAL
contributes directly to breast cancer progression. This study examines the relationship between
NGAL
expression in breast carcinomas and established clinical prognostic markers as well as clinical outcome. Using immunohistochemistry in tissue microarrays containing well characterized tumor samples from 207 breast cancer patients,
NGAL
was detected in 68 breast carcinomas in a cytoplasmic location.
NGAL
expression correlated strongly with negative steroid receptor status,
HER-2/neu
overexpression, poor histologic grade, the presence of lymph node metastases and a high Ki-67 proliferation index. In univariate survival analysis,
NGAL
expression was associated with decreased disease-specific survival and decreased disease-free survival in the entire cohort. In multivariate analysis,
NGAL
remained an independent prognostic marker for disease-free survival. In a subset of patients with estrogen receptor positive tumors,
NGAL
was significantly associated with decreased disease-free survival. The results show that
NGAL
expression is a predictor of poor prognosis in primary human breast cancer and suggest that
NGAL
detection may provide information for risk assessment and identify a subset of patients requiring more aggressive adjuvant therapy.
...
PMID:Neutrophil gelatinase-associated lipocalin (NGAL) is a predictor of poor prognosis in human primary breast cancer. 1755 27