Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2009-5-4
pubmed:abstractText
In previous studies on HeLa cells we demonstrated estrogen-responsiveness of the epidermal growth factor receptor (EGFR) gene, as 17beta-estradiol (E(2)) and selective estrogen receptor modulators (SERMs) genistein (G), daidzein (D), and 4-hydroxytamoxifen (4OH-T) modulated its transcription in a ligand- and estrogen receptor (ER) isoform-specific way. This study describes further investigations into the role of ERs in mediating the effects induced by E(2) and SERMs on EGFR expression, and the relationship between the actions of ERs and EGFR in U2OS osteosarcoma cells stably expressing ERalpha or ERbeta. Cell number and DNA content determination revealed that E(2), G, and D inhibited proliferation and cell cycle progression and promoted apoptosis in both cell lines. In parallel, changes in cell morphology typical of osteoblast maturation were observed via optical microscopy. Consistently, quantitative PCR and Western blot analysis showed an up-regulation of markers of osteoblast differentiation and bone repair, and a decrease in EGFR expression. The transfection of specific antisense (AS) oligonucleotides strengthened our hypothesis that EGFR reduction caused changes in the proliferation/differentiation pattern comparable to those induced by ER ligands. The link between the ER and EGFR pathways was confirmed by treatment with 4OH-T, which decreased the EGFR level and produced differentiation effects via ERalpha, but induced both EGFR expression and proliferation effects via ERbeta. In conclusion, we show that also in U2OS cells, E(2) and SERMs are able to modulate the expression of the EGFR gene and can affect events strictly controlled by its signaling pathway, such as the maturation of osteoblasts.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/4-hydroxytamoxifen, http://linkedlifedata.com/resource/pubmed/chemical/Biological Markers, http://linkedlifedata.com/resource/pubmed/chemical/EGFR protein, human, http://linkedlifedata.com/resource/pubmed/chemical/Estradiol, http://linkedlifedata.com/resource/pubmed/chemical/Estrogen Receptor alpha, http://linkedlifedata.com/resource/pubmed/chemical/Estrogen Receptor beta, http://linkedlifedata.com/resource/pubmed/chemical/Genistein, http://linkedlifedata.com/resource/pubmed/chemical/Isoflavones, http://linkedlifedata.com/resource/pubmed/chemical/Phytoestrogens, http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger, http://linkedlifedata.com/resource/pubmed/chemical/Receptor, Epidermal Growth Factor, http://linkedlifedata.com/resource/pubmed/chemical/Selective Estrogen Receptor..., http://linkedlifedata.com/resource/pubmed/chemical/Tamoxifen, http://linkedlifedata.com/resource/pubmed/chemical/daidzein
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
1097-4652
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
220
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
35-44
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:19347870-Apoptosis, pubmed-meshheading:19347870-Biological Markers, pubmed-meshheading:19347870-Cell Cycle, pubmed-meshheading:19347870-Cell Differentiation, pubmed-meshheading:19347870-Cell Line, Tumor, pubmed-meshheading:19347870-Cell Proliferation, pubmed-meshheading:19347870-Cell Shape, pubmed-meshheading:19347870-Down-Regulation, pubmed-meshheading:19347870-Estradiol, pubmed-meshheading:19347870-Estrogen Receptor alpha, pubmed-meshheading:19347870-Estrogen Receptor beta, pubmed-meshheading:19347870-Genistein, pubmed-meshheading:19347870-Humans, pubmed-meshheading:19347870-Isoflavones, pubmed-meshheading:19347870-Osteoblasts, pubmed-meshheading:19347870-Osteosarcoma, pubmed-meshheading:19347870-Phytoestrogens, pubmed-meshheading:19347870-RNA, Messenger, pubmed-meshheading:19347870-Receptor, Epidermal Growth Factor, pubmed-meshheading:19347870-Selective Estrogen Receptor Modulators, pubmed-meshheading:19347870-Tamoxifen, pubmed-meshheading:19347870-Time Factors
pubmed:year
2009
pubmed:articleTitle
Down-regulation of epidermal growth factor receptor induced by estrogens and phytoestrogens promotes the differentiation of U2OS human osteosarcoma cells.
pubmed:affiliation
Department of Experimental Medicine, Sapienza University of Rome, Rome, Italy. luisa.salvatori@ifo.it
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't