Linked Life Data

10519397

Source:http://linkedlifedata.com/resource/pubmed/id/10519397

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
19
pubmed:dateCreated
1999-11-4
pubmed:abstractText
Estrogens stimulate the proliferation of many breast tumors and cell lines derived from them. Antiestrogens have therefore become a powerful therapeutic agent to treat breast tumors that express estrogen receptor (ER) alpha. In addition, aromatase inhibitors are now used in postmenopausal women to block the in situ conversion of adrenal androgens to estrogens. This approach can only be successful if ER-alpha in a particular tumor is not directly stimulated by adrenal androgens. We have examined this possibility using several different cell lines as model systems: (a) wild-type MCF7 cells, an ER-alpha-dependent human breast cancer cell line; (b) MCF7SH cells, an estrogen-independent MCF7 variant; (c) Ishikawa cells, an ER-alpha-containing human uterine cell line; (d) ER-negative HeLa cells; and (e) budding yeast. Transactivation assays with transfected ER-alpha reporter genes reveal a direct activation of ER-alpha by dehydroepiandrosterone (DHEA), 5alpha-androstene-3beta,17beta-diol, testosterone, and the two nonaromatizable androgens, dihydrotestosterone and 5alpha-androstane-3beta,17beta-diol. The involvement of other steroid receptors could be ruled out with specific antihormones. Moreover, the same set of ligands stimulates the proliferation of the two breast cancer cell lines. At subsaturating and physiologically relevant concentrations of DHEA, DHEA stimulates the proliferation of MCF7SH cells, which correlates with a substantial, albeit submaximal, transcriptional response. Thus, adrenal androgens must also be considered as risk factors in postmenopausal women.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0008-5472
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
59
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
4864-9
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:10519397-Androgens, pubmed-meshheading:10519397-Androstenediol, pubmed-meshheading:10519397-Breast Neoplasms, pubmed-meshheading:10519397-Cell Division, pubmed-meshheading:10519397-Cloning, Molecular, pubmed-meshheading:10519397-Dehydroepiandrosterone, pubmed-meshheading:10519397-Dihydrotestosterone, pubmed-meshheading:10519397-Estrogen Receptor alpha, pubmed-meshheading:10519397-Female, pubmed-meshheading:10519397-Genes, Reporter, pubmed-meshheading:10519397-HeLa Cells, pubmed-meshheading:10519397-Humans, pubmed-meshheading:10519397-Luciferases, pubmed-meshheading:10519397-Receptors, Estrogen, pubmed-meshheading:10519397-Recombinant Fusion Proteins, pubmed-meshheading:10519397-Saccharomyces cerevisiae, pubmed-meshheading:10519397-Testosterone, pubmed-meshheading:10519397-Transfection, pubmed-meshheading:10519397-Tumor Cells, Cultured, pubmed-meshheading:10519397-Uterus
pubmed:year
1999
pubmed:articleTitle
Adrenal androgens stimulate the proliferation of breast cancer cells as direct activators of estrogen receptor alpha.
pubmed:affiliation
Département de Biologie Cellulaire, Université de Genève, Switzerland.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't