Linked Life Data

16925584

Source:http://linkedlifedata.com/resource/pubmed/id/16925584

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
11
pubmed:dateCreated
2006-10-12
pubmed:abstractText
The human multidrug resistance gene 1 (MDR1) encodes the plasma membrane P-glycoprotein (P-gp/ABCB1) that functions as an efflux pump for various anticancer agents. We recently reported that estrogens down-regulate the expression of breast cancer resistance protein (BCRP/ABCG2). In our present study we demonstrate that estrogens also down-regulate P-gp expression in the MDR1-transduced, estrogen receptor alpha (ER-alpha)-positive human breast cancer cells, MCF-7/MDR and T-47D/MDR. The P-gp expression levels in MCF-7/MDR cells treated with 100 pM estradiol were found to be 10-20-fold lower than the levels in these same cells that were cultured without estradiol. In contrast, estradiol did not affect the P-gp expression levels in the ER-alpha-negative cancer cells, MDA-MB-231/MDR and NCI/ADR-RES. Estrone and diethylstilbestrol were also found to down-regulate P-gp in MCF-7/MDR cells, but progesterone treatment did not produce this effect. Tamoxifen reversed the estradiol-mediated down-regulation of P-gp in MCF-7/MDR cells, suggesting that ER-alpha activity is necessary for the effects of estradiol upon P-gp. However, estradiol was found not to alter the MDR1 transcript levels in either MCF-7/MDR and T-47D/MDR cells, suggesting that post-transcriptional mechanisms underlie its effects upon P-gp down-regulation. MCF-7/MDR cells also showed eight-fold higher sensitivity to vincristine when treated with 100 pM estradiol, than when treated with 1 pM estradiol. These results may serve to provide a better understanding of the expression control of ABC transporters, and possibly allow for the establishment of new cancer chemotherapy strategies that would control P-gp expression in breast cancer cells and thereby increase their sensitivity to MDR1-related anticancer agents.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
1347-9032
pubmed:author
pubmed:issnType
Print
pubmed:volume
97
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1198-204
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:16925584-Antineoplastic Agents, Phytogenic, pubmed-meshheading:16925584-Biological Transport, pubmed-meshheading:16925584-Blotting, Western, pubmed-meshheading:16925584-Breast Neoplasms, pubmed-meshheading:16925584-Cell Line, Tumor, pubmed-meshheading:16925584-Down-Regulation, pubmed-meshheading:16925584-Drug Resistance, Neoplasm, pubmed-meshheading:16925584-Estradiol, pubmed-meshheading:16925584-Estrogen Receptor alpha, pubmed-meshheading:16925584-Estrogens, pubmed-meshheading:16925584-Flow Cytometry, pubmed-meshheading:16925584-Gene Expression Regulation, Neoplastic, pubmed-meshheading:16925584-Genes, MDR, pubmed-meshheading:16925584-Humans, pubmed-meshheading:16925584-Neoplasms, Hormone-Dependent, pubmed-meshheading:16925584-P-Glycoprotein, pubmed-meshheading:16925584-Reverse Transcriptase Polymerase Chain Reaction, pubmed-meshheading:16925584-Tamoxifen, pubmed-meshheading:16925584-Transduction, Genetic, pubmed-meshheading:16925584-Tumor Cells, Cultured, pubmed-meshheading:16925584-Vincristine
pubmed:year
2006
pubmed:articleTitle
Estrogen-mediated post transcriptional down-regulation of P-glycoprotein in MDR1-transduced human breast cancer cells.
pubmed:affiliation
Department of Chemotherapy, Kyoritsu University of Pharmacy, 1-5-30 Shibakoen, Minatoku, Tokyo 105-8512, Japan.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't