Linked Life Data

20730598

Source:http://linkedlifedata.com/resource/pubmed/id/20730598

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2011-6-20
pubmed:abstractText
Estrogen receptor-? (ER?) positive breast cancer frequently responds to inhibitors of ER? activity, such as tamoxifen, and/or to aromatase inhibitors that block estrogen biosynthesis. However, many patients become resistant to these agents through mechanisms that remain unclear. Previous studies have shown that expression of ER? in ER?-negative breast cancer cell lines frequently inhibits their growth. In order to determine the consequence of ER? over-expression in ER?-positive breast cancer cells, we over-expressed ER? in the MCF-7 breast cancer cell line using adenovirus gene transduction. ER? over-expression led to ligand-independent expression of the estrogen-regulated genes pS2 and PR and growth in the absence of estrogen. Interestingly, prolonged culturing of these cells in estrogen-free conditions led to the outgrowth of cells capable of growth in cultures from ER? transduced, but not in control cultures. From these cultures a line, MLET5, was established which remained ER?-positive, but grew in an estrogen-independent manner. Moreover, MLET5 cells were inhibited by anti-estrogens showing that ER? remains important for their growth. Gene expression microarray analysis comparing MCF-7 cells with MLET5 highlighted apoptosis as a major functional grouping that is altered in MLET5 cells, such that cell survival would be favoured. This conclusion was further substantiated by the demonstration that MLET5 show resistance to etoposide-induced apoptosis. As the gene expression microarray analysis also shows that the apoptosis gene set differentially expressed in MLET5 is enriched for estrogen-regulated genes, our findings suggest that transient over-expression of ER? could lead to increased cell survival and the development of estrogen-independent growth, thereby contributing to resistance to endocrine therapies in breast cancer patients.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
1573-7217
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
128
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
357-68
pubmed:meshHeading
pubmed-meshheading:20730598-Adenoviridae, pubmed-meshheading:20730598-Antineoplastic Agents, Hormonal, pubmed-meshheading:20730598-Apoptosis, pubmed-meshheading:20730598-Blotting, Western, pubmed-meshheading:20730598-Breast Neoplasms, pubmed-meshheading:20730598-Cell Cycle, pubmed-meshheading:20730598-Cell Proliferation, pubmed-meshheading:20730598-Drug Resistance, Neoplasm, pubmed-meshheading:20730598-Estrogen Receptor alpha, pubmed-meshheading:20730598-Estrogens, pubmed-meshheading:20730598-Female, pubmed-meshheading:20730598-Gene Expression Profiling, pubmed-meshheading:20730598-Gene Expression Regulation, Neoplastic, pubmed-meshheading:20730598-Humans, pubmed-meshheading:20730598-Oligonucleotide Array Sequence Analysis, pubmed-meshheading:20730598-RNA, Messenger, pubmed-meshheading:20730598-Reverse Transcriptase Polymerase Chain Reaction, pubmed-meshheading:20730598-Tamoxifen, pubmed-meshheading:20730598-Tumor Cells, Cultured, pubmed-meshheading:20730598-Tumor Markers, Biological
pubmed:year
2011
pubmed:articleTitle
Transient over-expression of estrogen receptor-? in breast cancer cells promotes cell survival and estrogen-independent growth.
pubmed:affiliation
Division of Cancer, Department of Surgery & Cancer, Imperial College London, Hammersmith Hospital Campus, Du Cane Road, London W12 0NN, UK.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't