Linked Life Data

15645127

Source:http://linkedlifedata.com/resource/pubmed/id/15645127

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2005-1-12
pubmed:abstractText
Prolonged unopposed estrogen exposure is a widely accepted risk factor in breast cancer development. However, the mechanisms through which estrogens induce breast carcinogenesis have not been definitively unraveled. For testing whether estrogens exert their transforming effects through a non-receptor-mediated mechanism, we have treated the spontaneously immortalized human breast epithelial cells MCF-10F, which are estrogen receptor alpha negative, with 17-beta estradiol (E(2)) or its metabolite 4-OH-estradiol (4-OH-E(2)), each one either alone or in combination with the antiestrogen ICI-182-780. Treated cells were maintained for several passages in culture and evaluated for colony formation in agar-methocel (CE), tri-dimensional growth in collagen matrix, invasiveness in matrigel, and cell cycle analysis by flow cytometry. Both E(2) and 4-HO-E(2), at all the doses tested, in the presence or absence of ICI-182-780, increased CE and decreased the cells' ductulogenic capacity. They also increased the invasiveness and the number of cells in the S phase of the cell cycle. Our data clearly demonstrate that E(2) and 4-OH-E(2) increase cell proliferation and induce transformation in MCF-10F cells, phenomena that are not abrogated by ICI-182-780. The failure of the antiestrogen to abrogate the transformation phenotypes led us to hypothesize that estrogen-induced transformation is occurring by a non-estrogen receptor alpha-mediated process, more probably through the genotoxic effect of the estrogen metabolite 4-HO-E(2).
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
1019-6439
pubmed:author
pubmed:issnType
Print
pubmed:volume
26
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
423-9
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:15645127-Agar, pubmed-meshheading:15645127-Breast, pubmed-meshheading:15645127-Cell Cycle, pubmed-meshheading:15645127-Cell Line, pubmed-meshheading:15645127-Cell Line, Tumor, pubmed-meshheading:15645127-Cell Proliferation, pubmed-meshheading:15645127-Collagen, pubmed-meshheading:15645127-Dose-Response Relationship, Drug, pubmed-meshheading:15645127-Drug Combinations, pubmed-meshheading:15645127-Epithelial Cells, pubmed-meshheading:15645127-Estradiol, pubmed-meshheading:15645127-Estrogen Receptor alpha, pubmed-meshheading:15645127-Estrogens, pubmed-meshheading:15645127-Female, pubmed-meshheading:15645127-Flow Cytometry, pubmed-meshheading:15645127-G0 Phase, pubmed-meshheading:15645127-G1 Phase, pubmed-meshheading:15645127-Humans, pubmed-meshheading:15645127-Laminin, pubmed-meshheading:15645127-Neoplasm Invasiveness, pubmed-meshheading:15645127-Phenotype, pubmed-meshheading:15645127-Proteoglycans
pubmed:year
2005
pubmed:articleTitle
The estrogen antagonist ICI-182-780 does not inhibit the transformation phenotypes induced by 17-beta-estradiol and 4-OH estradiol in human breast epithelial cells.
pubmed:affiliation
Breast Cancer Research Laboratory, Fox Chase Cancer Center, Philadelphia, PA 19111, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, Non-P.H.S.