Linked Life Data

9634005

Source:http://linkedlifedata.com/resource/pubmed/id/9634005

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
10
pubmed:dateCreated
1998-7-2
pubmed:abstractText
Human RFC1 (hRFC1) transfected in transport-deficient methotrexate MTXR(R)ZR-75-1 human breast carcinoma cells (MTX(R)ZR-75/RFC) were used to investigate the impact of hRFC1 overexpression on influx and concentrative transport of methotrexate (MTX). Eight-fold overexpression of hRFC1, as determined by northern analysis, resulted in a 4-fold increase in MTX influx accompanied by a 2.4-fold increase in the steady-state level of free drug as compared with wild-type ZR-75-1 cells when the extracellular MTX level was 0.5 microM. When extracellular MTX was increased to 10 microM, the increase in influx equaled the increase in the transmembrane chemical gradient for MTX in the transfectant relative to wild-type cells. By 50 min, approximately 16-20 and 25% of the intracellular 3H represented MTX polyglutamates by HPLC analysis at [MTX]e = 0.5 and 10 microM in wild-type and transfected cells, respectively. Overexpression of hRFC1 enhanced sensitivity to MTX in MTX(R)ZR-75-1 cells by more than 250-fold. The data indicate that overexpression of hRFC1 in human cells results in comparable increases in influx and transmembrane gradients. This is different from what was reported when mouse RFC1 was transfected into murine leukemia cells, resulting in large, more symmetrical increases in the MTX bidirectional transport kinetics with a much smaller change in steady-state levels. The changes in the human cells transfected with hRFC1 however, were similar to what has been observed by other investigators when RFC1 expression is increased by low folate selective pressure.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/Antimetabolites, Antineoplastic, http://linkedlifedata.com/resource/pubmed/chemical/Carrier Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Folic Acid, http://linkedlifedata.com/resource/pubmed/chemical/Membrane Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Membrane Transport Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Methotrexate, http://linkedlifedata.com/resource/pubmed/chemical/Reduced Folate Carrier Protein, http://linkedlifedata.com/resource/pubmed/chemical/SLC19A1 protein, human, http://linkedlifedata.com/resource/pubmed/chemical/SLC19A2 protein, human, http://linkedlifedata.com/resource/pubmed/chemical/Slc19a1 protein, mouse, http://linkedlifedata.com/resource/pubmed/chemical/Slc19a2 protein, mouse
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0006-2952
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
55
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1683-9
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed:year
1998
pubmed:articleTitle
Concentrating capacity of the human reduced folate carrier (hRFC1) in human ZR-75 breast cancer cell lines.
pubmed:affiliation
Department of Medicine, Albert Einstein Comprehensive Cancer Center, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.