rdf:type |
|
lifeskim:mentions |
umls-concept:C0006141,
umls-concept:C0014597,
umls-concept:C0017337,
umls-concept:C0035820,
umls-concept:C0051755,
umls-concept:C0085862,
umls-concept:C0086418,
umls-concept:C0205245,
umls-concept:C0205263,
umls-concept:C0242275,
umls-concept:C0430054,
umls-concept:C0929301,
umls-concept:C1456348,
umls-concept:C1705053
|
pubmed:issue |
30
|
pubmed:dateCreated |
2001-8-8
|
pubmed:abstractText |
To gain better understanding of the molecular alterations responsible for the aggressive growth potential of epidermal growth factor receptor (EGFR)-positive breast cancers, we utilized an expression cloning strategy to seek gene products that mediate the EGF-independent growth of human breast cancer cells. A retroviral cDNA expression library was constructed from the EGFR-positive SUM-149PT cell line, and transduced into growth factor-dependent human mammary epithelial (HME) cells. Recipient cells were functionally selected for their ability to proliferate in serum-free, EGF-free medium. Library cDNAs were recovered from EGF-independent colonies by PCR amplification or by biological rescue. Clone H55a#1 contained a library insert encoding amphiregulin. This EGFR ligand was able to confer EGF independence when transduced into HME cells. SUM-149PT and H55a#1 cells overexpressed amphiregulin transcripts, and secreted moderate EGF-like activity in conditioned media, indicating a possible autocrine loop. EGFR membrane levels and constitutive phosphorylation were consistent with this hypothesis, as well as the sensitivity of the cells to an ErbB-specific kinase inhibitor. Expression of the WT1 Wilms' tumor suppressor gene, a transcriptional activator of amphiregulin, did not parallel amphiregulin transcript levels, suggesting that another factor regulates amphiregulin in SUM-149PT. Our data confirm the importance of amphiregulin in the etiology of breast cancer.
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pubmed:grant |
|
pubmed:language |
eng
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pubmed:journal |
|
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Culture Media, Conditioned,
http://linkedlifedata.com/resource/pubmed/chemical/Culture Media, Serum-Free,
http://linkedlifedata.com/resource/pubmed/chemical/DNA, Complementary,
http://linkedlifedata.com/resource/pubmed/chemical/Epidermal Growth Factor,
http://linkedlifedata.com/resource/pubmed/chemical/Glycoproteins,
http://linkedlifedata.com/resource/pubmed/chemical/Growth Substances,
http://linkedlifedata.com/resource/pubmed/chemical/Intercellular Signaling Peptides...,
http://linkedlifedata.com/resource/pubmed/chemical/Neoplasm Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Receptor, Epidermal Growth Factor,
http://linkedlifedata.com/resource/pubmed/chemical/amphiregulin
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pubmed:status |
MEDLINE
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pubmed:month |
Jul
|
pubmed:issn |
0950-9232
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pubmed:author |
|
pubmed:issnType |
Print
|
pubmed:day |
5
|
pubmed:volume |
20
|
pubmed:owner |
NLM
|
pubmed:authorsComplete |
Y
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pubmed:pagination |
4019-28
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:11494130-Breast,
pubmed-meshheading:11494130-Breast Neoplasms,
pubmed-meshheading:11494130-Cell Division,
pubmed-meshheading:11494130-Cell Transformation, Neoplastic,
pubmed-meshheading:11494130-Cells, Cultured,
pubmed-meshheading:11494130-Clone Cells,
pubmed-meshheading:11494130-Culture Media, Conditioned,
pubmed-meshheading:11494130-Culture Media, Serum-Free,
pubmed-meshheading:11494130-DNA, Complementary,
pubmed-meshheading:11494130-Epidermal Growth Factor,
pubmed-meshheading:11494130-Epithelial Cells,
pubmed-meshheading:11494130-Female,
pubmed-meshheading:11494130-Gene Library,
pubmed-meshheading:11494130-Genes, Wilms Tumor,
pubmed-meshheading:11494130-Genetic Complementation Test,
pubmed-meshheading:11494130-Genetic Techniques,
pubmed-meshheading:11494130-Genetic Vectors,
pubmed-meshheading:11494130-Glycoproteins,
pubmed-meshheading:11494130-Growth Substances,
pubmed-meshheading:11494130-Humans,
pubmed-meshheading:11494130-Intercellular Signaling Peptides and Proteins,
pubmed-meshheading:11494130-Neoplasm Proteins,
pubmed-meshheading:11494130-Neoplastic Stem Cells,
pubmed-meshheading:11494130-Phenotype,
pubmed-meshheading:11494130-Receptor, Epidermal Growth Factor,
pubmed-meshheading:11494130-Retroviridae,
pubmed-meshheading:11494130-Transfection,
pubmed-meshheading:11494130-Tumor Cells, Cultured
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pubmed:year |
2001
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pubmed:articleTitle |
A functional screen for genes inducing epidermal growth factor autonomy of human mammary epithelial cells confirms the role of amphiregulin.
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pubmed:affiliation |
Department of Radiation Oncology, Division of Radiation and Cancer Biology, University of Michigan, Ann Arbor, Michigan, MI 48109, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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