Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
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.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0950-9232
pubmed:author
pubmed:issnType
Print
pubmed:day
5
pubmed:volume
20
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
4019-28
pubmed:dateRevised
2009-11-19
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
pubmed:year
2001
pubmed:articleTitle
A functional screen for genes inducing epidermal growth factor autonomy of human mammary epithelial cells confirms the role of amphiregulin.
pubmed:affiliation
Department of Radiation Oncology, Division of Radiation and Cancer Biology, University of Michigan, Ann Arbor, Michigan, MI 48109, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't