Linked Life Data

15958587

Source:http://linkedlifedata.com/resource/pubmed/id/15958587

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
12
pubmed:dateCreated
2005-6-16
pubmed:abstractText
Ovariectomized mice bearing tumor xenografts grown from aromatase-transfected estrogen receptor (ER)-positive human breast cancer cells (MCF-7Ca) were injected s.c. with 10 microg/d letrozole for up to 56 weeks. Western blot analysis of the tumors revealed that ERs (ERalpha) were increased at 4 weeks but decreased at weeks 28 and 56. Expression of erbB-2 and p-Shc increased throughout treatment, whereas growth factor receptor binding protein 2 (Grb2) increased only in tumors proliferating on letrozole (weeks 28 and 56). In cells isolated from tumors after 56 weeks and maintained as a cell line (LTLT-Ca) in 1 micromol/L letrozole, ERalpha was also decreased whereas erbB-2, adapter proteins (p-Shc and Grb2), and the signaling proteins in the mitogen-activated protein kinase (MAPK) cascade were increased compared with MCF-7Ca cells. Growth was inhibited in LTLT-Ca cells but not in MCF-7Ca cells treated with MAPK kinase 1/2 inhibitors U0126, and PD98059 (IC(50) approximately 25 micromol/L). PD98059 (5 micromol/L) also reduced MAPK activity and increased ERalpha to the levels in MCF-7Ca cells. Epidermal growth factor receptor kinase inhibitor, gefitinib (ZD1839) inhibited growth of LTLT-Ca cells (IC(50) approximately 10 micromol/L) and restored their sensitivity to tamoxifen and anastrozole. In xenografts, combined treatment with ER down-regulator fulvestrant and letrozole, prevented increases in erbB-2 and activation of MAPK and was highly effective in inhibiting tumor growth throughout 29 weeks of treatment. These results indicate that blocking both ER- and growth factor-mediated transcription resulted in the most effective inhibition of growth of ER-positive breast cancer cells.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0008-5472
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
65
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
5380-9
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:15958587-Animals, pubmed-meshheading:15958587-Antineoplastic Combined Chemotherapy Protocols, pubmed-meshheading:15958587-Aromatase Inhibitors, pubmed-meshheading:15958587-Breast Neoplasms, pubmed-meshheading:15958587-Cell Line, Tumor, pubmed-meshheading:15958587-Drug Administration Schedule, pubmed-meshheading:15958587-Enzyme Activation, pubmed-meshheading:15958587-Estrogen Receptor alpha, pubmed-meshheading:15958587-Female, pubmed-meshheading:15958587-Humans, pubmed-meshheading:15958587-MAP Kinase Signaling System, pubmed-meshheading:15958587-Mice, pubmed-meshheading:15958587-Mice, Inbred BALB C, pubmed-meshheading:15958587-Mice, Nude, pubmed-meshheading:15958587-Mitogen-Activated Protein Kinases, pubmed-meshheading:15958587-Nitriles, pubmed-meshheading:15958587-Tamoxifen, pubmed-meshheading:15958587-Triazoles, pubmed-meshheading:15958587-Xenograft Model Antitumor Assays
pubmed:year
2005
pubmed:articleTitle
Activation of mitogen-activated protein kinase in xenografts and cells during prolonged treatment with aromatase inhibitor letrozole.
pubmed:affiliation
Department of Pharmacology and Experimental Therapeutics, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, N.I.H., Extramural