Linked Life Data

9831386

Source:http://linkedlifedata.com/resource/pubmed/id/9831386

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1-2
pubmed:dateCreated
1998-12-7
pubmed:abstractText
The epidermal growth factor receptor (ErbB1) is overexpressed in various human tumor-derived cell lines and neoplasms, where it is believed that receptor dysregulation plays a role in oncogenic transformation and tumor progression. In addition to the ErbB1 holoreceptor, numerous studies demonstrate that cells synthesize soluble or secreted forms of ErbB1, i.e., sErbB1. Overexpression of ErbB1 in a variety of tumors has led us to hypothesize that sErbB levels also may be altered during oncogenesis, tumor progression, and/or metastasis; and that these molecules may be useful tumor biomarkers. To address this hypothesis we have developed an acridinium-linked immunosorbent assay (ALISA) specific for the extracellular domain of ErbB1 that can be used to quantify the levels of sErbB1 molecules in body fluids and conditioned culture media. This assay can also detect full-length ErbB1 in cell and tissue extracts. Our ALISA is characterized by high sensitivity (intra-assay LLD < 1 fmol/ml), a broad linear range (approximately 1 to 4000 fmol/ml), and good reproducibility (CVs < 10%). Specificity experiments show that this ALISA detects p170 ErbB1 and soluble forms of ErbB1 that embody extracellular subdomains I through IV, but not forms of sErbB1 lacking subdomain IV. Our ALISA does not detect full-length ErbB2, ErbB3, or ErbB4; or p105 soluble ErbB2. We report that serum sErbB1 levels of healthy women (median = 3716 fmol/ml), ranging in age from 43 to 76 years, differ significantly from those of healthy men (median = 24,512 fmol/ml), ranging in age from 25 to 79 years. Additional analyses do not indicate that serum sErbB1 levels change with age in either healthy men or women. Immunoprecipitation experiments show that monoclonal antibodies specific for extracellular epitopes of ErbB1 completely neutralize the detection of sErbB1 in normal human sera by ALISA. Finally, we show by immunoprecipitation and Western immunoblot analyses with monoclonal antibodies specific for the extracellular domain of ErbB1 that normal human female and male sera contain a approximately 110-kDa protein. We conclude that our ALISA is measuring the relative levels of this p110 sErbB1 analog in normal human sera. Our ALISA, therefore, should be useful for measuring the levels of ErbB1 and sErbB1 molecules in tumor biopsy specimens and body fluids, respectively, and for determining whether sErbB1, like ErbB1, is a useful tumor biomarker.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0022-1759
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
219
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
23-43
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:9831386-Acridines, pubmed-meshheading:9831386-Adult, pubmed-meshheading:9831386-Aged, pubmed-meshheading:9831386-Blotting, Western, pubmed-meshheading:9831386-Enzyme-Linked Immunosorbent Assay, pubmed-meshheading:9831386-Female, pubmed-meshheading:9831386-Humans, pubmed-meshheading:9831386-Immunosorbent Techniques, pubmed-meshheading:9831386-Male, pubmed-meshheading:9831386-Middle Aged, pubmed-meshheading:9831386-Precipitin Tests, pubmed-meshheading:9831386-Protein Isoforms, pubmed-meshheading:9831386-Receptor, Epidermal Growth Factor, pubmed-meshheading:9831386-Recombinant Proteins, pubmed-meshheading:9831386-Reference Values, pubmed-meshheading:9831386-Reproducibility of Results, pubmed-meshheading:9831386-Sensitivity and Specificity, pubmed-meshheading:9831386-Solubility, pubmed-meshheading:9831386-Tumor Cells, Cultured, pubmed-meshheading:9831386-Tumor Markers, Biological
pubmed:year
1998
pubmed:articleTitle
A sandwich type acridinium-linked immunosorbent assay (ALISA) detects soluble ErbB1 (sErbB1) in normal human sera.
pubmed:affiliation
Tumor Biology Program, Mayo Clinic, Rochester, MN 55905, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't