Source:http://linkedlifedata.com/resource/pubmed/id/15767552
Switch to
| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
3
|
| pubmed:dateCreated |
2005-3-15
|
| pubmed:abstractText |
Inactivation of epidermal growth factor receptor (EGFR) family members represents a promising strategy for the development of selective therapies against epithelial cancers. Current anti-EGFR therapies, such as cetuximab (Erbitux), gefitinib (Iressa), or trastuzumab (Herceptin), target EGFR or HER-2 but not both. Because solid tumors express different EGFRs, identification of inhibitor(s), targeting multiple EGFR family members may provide a therapeutic benefit to a broader patient population. We have identified a natural inhibitor of EGFRs called EGFR-related protein (ERRP), a 53 to 55 kDa protein that is present in most, if not all, normal human epithelial cells. The growth of colon (HCT-116, Caco2, and HT-29) and breast (MDA-MB-468 and SKBR-3) cancer cells expressing varying levels of EGFR, HER-2, and/or HER-4 was inhibited by recombinant ERRP in a dose-dependent manner. In contrast, ERRP caused no inhibition of growth of normal mouse fibroblast cell lines (NIH-3T3, NIH-3T3/P67), and the growth of nontransformed rat small intestinal IEC-6 cells expressing relatively low levels of EGFRs was inhibited only at high doses of ERRP. Transforming growth factor-alpha or heparin-binding epidermal growth factor-induced activation of EGFR and HER-2 was inhibited by ERRP in colon and breast cancer cells expressing high levels of EGFR or HER-2. In contrast, cetuximab inhibited the growth- and ligand-induced activation of EGFR in cell lines expressing high levels of EGFR, whereas trastuzumab was effective only in HER-2-overexpressing cells. ERRP and trastuzumab, but not cetuximab, attenuated heregulin-alpha-induced activation of colon and breast cancer cells that expressed high levels of HER-2. Furthermore, ERRP, but not cetuximab or trastuzumab, significantly induced apoptosis of colon and breast cancer cells. None of these agents induced apoptosis of either NIH-3T3 mouse fibroblast or normal rat small intestinal IEC cells. Our results suggest that ERRP is an effective pan-erbB inhibitor and, thus, may be a potential therapeutic agent for a wide variety of epithelial cancers expressing different levels and subclasses of EGFRs.
|
| pubmed:grant | |
| pubmed:commentsCorrections | |
| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Antibodies, Monoclonal,
http://linkedlifedata.com/resource/pubmed/chemical/Antibodies, Monoclonal, Humanized,
http://linkedlifedata.com/resource/pubmed/chemical/Antineoplastic Agents,
http://linkedlifedata.com/resource/pubmed/chemical/Glycoproteins,
http://linkedlifedata.com/resource/pubmed/chemical/Ligands,
http://linkedlifedata.com/resource/pubmed/chemical/Neuregulin-1,
http://linkedlifedata.com/resource/pubmed/chemical/Receptor, Epidermal Growth Factor,
http://linkedlifedata.com/resource/pubmed/chemical/Receptor, erbB-2,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Fusion Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Tyrosine,
http://linkedlifedata.com/resource/pubmed/chemical/cetuximab,
http://linkedlifedata.com/resource/pubmed/chemical/epidermal growth factor receptor...,
http://linkedlifedata.com/resource/pubmed/chemical/heregulin alpha,
http://linkedlifedata.com/resource/pubmed/chemical/trastuzumab
|
| pubmed:status |
MEDLINE
|
| pubmed:month |
Mar
|
| pubmed:issn |
1535-7163
|
| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:volume |
4
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
435-42
|
| pubmed:dateRevised |
2011-11-17
|
| pubmed:meshHeading |
pubmed-meshheading:15767552-Animals,
pubmed-meshheading:15767552-Antibodies, Monoclonal,
pubmed-meshheading:15767552-Antibodies, Monoclonal, Humanized,
pubmed-meshheading:15767552-Antineoplastic Agents,
pubmed-meshheading:15767552-Apoptosis,
pubmed-meshheading:15767552-Blotting, Western,
pubmed-meshheading:15767552-Breast Neoplasms,
pubmed-meshheading:15767552-Cell Line, Tumor,
pubmed-meshheading:15767552-Cells, Cultured,
pubmed-meshheading:15767552-Colonic Neoplasms,
pubmed-meshheading:15767552-Dose-Response Relationship, Drug,
pubmed-meshheading:15767552-Glycoproteins,
pubmed-meshheading:15767552-Humans,
pubmed-meshheading:15767552-Ligands,
pubmed-meshheading:15767552-Mice,
pubmed-meshheading:15767552-NIH 3T3 Cells,
pubmed-meshheading:15767552-Neuregulin-1,
pubmed-meshheading:15767552-Phosphorylation,
pubmed-meshheading:15767552-Rats,
pubmed-meshheading:15767552-Receptor, Epidermal Growth Factor,
pubmed-meshheading:15767552-Receptor, erbB-2,
pubmed-meshheading:15767552-Recombinant Fusion Proteins,
pubmed-meshheading:15767552-Tyrosine
|
| pubmed:year |
2005
|
| pubmed:articleTitle |
Epidermal growth factor receptor (EGFR)-related protein inhibits multiple members of the EGFR family in colon and breast cancer cells.
|
| pubmed:affiliation |
John D. Dingell Veterans Affairs Medical Center, 4646 John R, Room B-4238, Detroit, MI 48201, USA.
|
| pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, U.S. Gov't, Non-P.H.S.,
Research Support, N.I.H., Extramural
|