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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
26
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pubmed:dateCreated |
2005-6-16
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pubmed:abstractText |
The majority (75%) of human breast cancers express estrogen receptor (ER). Although ER-positive tumors usually respond to antiestrogen therapies, 30% of them do not. It is not known what controls the ER status of breast cancers or their responsiveness to antihormone interventions. In this report, we document that transgenic (TG) expression of Wnt-1 in mice induces ER-positive tumors. Loss of Pten or gain of Ras mutations during the evolution of tumors in Wnt-1 TG mice has no effect on the expression of ER, but overexpression of Neu or loss of p53 leads to ER-negative tumors. Thus, our results provide compelling evidence that expression of ER in breast cancer may be influenced by specific genetic changes that promote cancer progression. These findings constitute a first step to explore the molecular mechanisms leading to ER-positive or ER-negative mammary tumors. In addition, we find that ER-positive tumors arising in Wnt-1 TG mice are refractory to both ovariectomy and the ER antagonist tamoxifen, but lose ER expression with tamoxifen, suggesting that antiestrogen selects for ER-negative tumor cells and that the ER-positive cell fraction is dispensable for growth of these tumors. This is a first report of a mouse model of antiestrogen-resistant ER-positive breast cancers, and could provide a powerful tool to study the molecular mechanisms that control antiestrogen resistance.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Antineoplastic Agents, Hormonal,
http://linkedlifedata.com/resource/pubmed/chemical/Intercellular Signaling Peptides...,
http://linkedlifedata.com/resource/pubmed/chemical/Mitogens,
http://linkedlifedata.com/resource/pubmed/chemical/PTEN Phosphohydrolase,
http://linkedlifedata.com/resource/pubmed/chemical/PTEN protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphoric Monoester Hydrolases,
http://linkedlifedata.com/resource/pubmed/chemical/Protein-Tyrosine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Receptor, erbB-2,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Estrogen,
http://linkedlifedata.com/resource/pubmed/chemical/Tamoxifen,
http://linkedlifedata.com/resource/pubmed/chemical/Tumor Suppressor Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/WNT1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Wnt Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Wnt1 Protein,
http://linkedlifedata.com/resource/pubmed/chemical/Wnt1 protein, mouse
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pubmed:status |
MEDLINE
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pubmed:month |
Jun
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pubmed:issn |
0950-9232
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
16
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pubmed:volume |
24
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
4220-31
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:15824740-Animals,
pubmed-meshheading:15824740-Antineoplastic Agents, Hormonal,
pubmed-meshheading:15824740-Breast Neoplasms,
pubmed-meshheading:15824740-Disease Models, Animal,
pubmed-meshheading:15824740-Drug Resistance, Neoplasm,
pubmed-meshheading:15824740-Gene Expression Regulation, Neoplastic,
pubmed-meshheading:15824740-Genes, p53,
pubmed-meshheading:15824740-Humans,
pubmed-meshheading:15824740-Immunohistochemistry,
pubmed-meshheading:15824740-Intercellular Signaling Peptides and Proteins,
pubmed-meshheading:15824740-Mammary Neoplasms, Animal,
pubmed-meshheading:15824740-Mice,
pubmed-meshheading:15824740-Mice, Transgenic,
pubmed-meshheading:15824740-Mitogens,
pubmed-meshheading:15824740-Ovariectomy,
pubmed-meshheading:15824740-PTEN Phosphohydrolase,
pubmed-meshheading:15824740-Phosphoric Monoester Hydrolases,
pubmed-meshheading:15824740-Protein-Tyrosine Kinases,
pubmed-meshheading:15824740-Receptor, erbB-2,
pubmed-meshheading:15824740-Receptors, Estrogen,
pubmed-meshheading:15824740-Signal Transduction,
pubmed-meshheading:15824740-Tamoxifen,
pubmed-meshheading:15824740-Tumor Suppressor Proteins,
pubmed-meshheading:15824740-Wnt Proteins,
pubmed-meshheading:15824740-Wnt1 Protein
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pubmed:year |
2005
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pubmed:articleTitle |
Estrogen receptor positivity in mammary tumors of Wnt-1 transgenic mice is influenced by collaborating oncogenic mutations.
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pubmed:affiliation |
Breast Center, Baylor College of Medicine, One Baylor Plaza, N1210.03, Houston, TX 77030, USA.
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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
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