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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
1
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pubmed:dateCreated |
1996-12-10
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pubmed:abstractText |
The erbB-2 oncoprotein is overexpressed in 30% of tumors from breast and ovarian cancer patients and it is related to poor overall and disease-free survival. In vitro studies on erbB-2-overexpressing cells have found a strong correlation between this oncogene overexpression and relative resistance to lymphokine-activated killer (LAK) cell lysis. gp30/heregulin/NDF (neu differentiation factor), indirect activators of erbB-2, are able to induce a more differentiated phenotype on erbB-2-overexpressing, erbB-3- and/or erbB-4-positive breast cancer cells. We tested the ability of these highly homologous growth factors to stimulate LAK cell lysis of breast cancer cells. Our experiments demonstrated a marked increase in LAK cell cytotoxicity towards an erbB-2-overexpressing, erbB-3-positive cell line by treatment of these cells with heregulin for 72 h. In contrast we did not observe any enhancement of lysis of MCF-7, a cell line that does not overexpress erbB-2 and is positive for the erbB-3 and erbB-4 receptors, after treatment with heregulin. The increased lysis was associated with upregulation of intercellular adhesion molecule 1 (ICAM-1), down-regulation of erbB-2 and increased binding between breast cancer cells and LAK cells. Pre incubation of target (SKBR3) cells with blocking anti-ICAM-1 antibody completely abrogated the enhanced cytotoxicity. A similar effect was observed by pretreatment of the effector (LAK) cells with antibodies directed against LFA-1, the receptor for ICAM-1. These results suggest the possible utilization of gp30/heregulin in the treatment of breast cancer patients by its ability to stimulate patient immune responses.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Glycoproteins,
http://linkedlifedata.com/resource/pubmed/chemical/Intercellular Adhesion Molecule-1,
http://linkedlifedata.com/resource/pubmed/chemical/Receptor, erbB-2,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/TGF-alpha-like 30-kDa...,
http://linkedlifedata.com/resource/pubmed/chemical/Transforming Growth Factor alpha
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pubmed:status |
MEDLINE
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pubmed:month |
Sep
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pubmed:issn |
0340-7004
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
43
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
19-25
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:8917631-Breast Neoplasms,
pubmed-meshheading:8917631-Female,
pubmed-meshheading:8917631-Gene Expression,
pubmed-meshheading:8917631-Glycoproteins,
pubmed-meshheading:8917631-Humans,
pubmed-meshheading:8917631-Intercellular Adhesion Molecule-1,
pubmed-meshheading:8917631-Killer Cells, Lymphokine-Activated,
pubmed-meshheading:8917631-Receptor, erbB-2,
pubmed-meshheading:8917631-Recombinant Proteins,
pubmed-meshheading:8917631-Transforming Growth Factor alpha,
pubmed-meshheading:8917631-Tumor Cells, Cultured
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pubmed:year |
1996
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pubmed:articleTitle |
Heregulin induces increase in sensitivity of an erbB-2-overexpressing breast cancer cell type to lysis by lymphokine-activated killer cells.
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pubmed:affiliation |
Vincent T. Lombardi Cancer Center, Georgetown University, Washington, DC 20007, USA.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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