Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2007-4-2
pubmed:abstractText
Steroid hormones such as 17beta-estradiol (E2) are critical to diverse cellular processes including tumorigenesis. A number of cofactors such as nuclear receptor corepressor (NCoR), CREB-binding protein (CBP), and steroid receptor coactivator 1 (SRC-1) interact with estrogen receptors (ERs) to regulate transcriptional repression or activation of target genes. Estrogen signaling in non-reproductive tract tissues such as skin is less well characterized and the effectiveness of anti-estrogen therapy for cancer arising from these tissues is unknown. We show that tamoxifen (TAM) treatment inhibited cell cycle progression and proliferation of human cancer lines derived from stratified squamous epithelium squamous cell carcinoma (SCC). E2 had no effect on proliferation of these lines despite low levels of ERalpha expression. The E2 treatment promoted displacement of the NCoR from ERalpha and recruitment of CBP to the receptor. SRC-1 expression was not detected in these SCC lines; however, transient transfection of SRC-1, CBP, or both coactivators enhanced transactivation of an estrogen responsive promoter in cancer cells treated with E2 or TAM. In stable clones expressing SRC-1, the coactivator was recruited to ERalpha along with CBP in E2 but not in TAM-treated cells. SRC-1 expression restored the E2-mediated proliferative response to human SCC lines. This increased proliferation correlated with increased extracellular signal regulated kinase 1 (ERK1) expression. SRC-1 and CBP were recruited to the proximal ERK1 promoter region in E2 but not in TAM-treated cells. We concluded that SRC-1 was a key molecular determinant of estrogen-mediated proliferation in human SCC lines.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/CREB-Binding Protein, http://linkedlifedata.com/resource/pubmed/chemical/CREBBP protein, human, http://linkedlifedata.com/resource/pubmed/chemical/Estrogen Antagonists, http://linkedlifedata.com/resource/pubmed/chemical/Estrogen Receptor alpha, http://linkedlifedata.com/resource/pubmed/chemical/Estrogens, http://linkedlifedata.com/resource/pubmed/chemical/Extracellular Signal-Regulated MAP..., http://linkedlifedata.com/resource/pubmed/chemical/Histone Acetyltransferases, http://linkedlifedata.com/resource/pubmed/chemical/Lipids, http://linkedlifedata.com/resource/pubmed/chemical/Lipofectamine, http://linkedlifedata.com/resource/pubmed/chemical/NCOA1 protein, human, http://linkedlifedata.com/resource/pubmed/chemical/Nuclear Receptor Coactivator 1, http://linkedlifedata.com/resource/pubmed/chemical/Tamoxifen, http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0022-0795
pubmed:author
pubmed:issnType
Print
pubmed:volume
193
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
147-55
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:17400812-Blotting, Western, pubmed-meshheading:17400812-Breast Neoplasms, pubmed-meshheading:17400812-CREB-Binding Protein, pubmed-meshheading:17400812-Carcinoma, Squamous Cell, pubmed-meshheading:17400812-Cell Cycle, pubmed-meshheading:17400812-Cell Line, Tumor, pubmed-meshheading:17400812-Cell Proliferation, pubmed-meshheading:17400812-Chromatin Immunoprecipitation, pubmed-meshheading:17400812-Estrogen Antagonists, pubmed-meshheading:17400812-Estrogen Receptor alpha, pubmed-meshheading:17400812-Estrogens, pubmed-meshheading:17400812-Extracellular Signal-Regulated MAP Kinases, pubmed-meshheading:17400812-Histone Acetyltransferases, pubmed-meshheading:17400812-Humans, pubmed-meshheading:17400812-Lipids, pubmed-meshheading:17400812-Nuclear Receptor Coactivator 1, pubmed-meshheading:17400812-Reverse Transcriptase Polymerase Chain Reaction, pubmed-meshheading:17400812-Tamoxifen, pubmed-meshheading:17400812-Transcription Factors, pubmed-meshheading:17400812-Transfection
pubmed:year
2007
pubmed:articleTitle
Coactivator-mediated estrogen response in human squamous cell carcinoma lines.
pubmed:affiliation
University of Illinois Cancer Center, Center for Molecular Biology of Oral Diseases, University of Illinois at Chicago, 801 South Paulina Street, Chicago, Illinois 60612, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't