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WFRF:(Al Khalili Szigyarto Cristina)
 

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LIBRIS Formathandbok  (Information om MARC21)
FältnamnIndikatorerMetadata
00004508naa a2200601 4500
001oai:DiVA.org:uu-107571
003SwePub
008090817s2009 | |||||||||||000 ||eng|
009oai:DiVA.org:kth-18970
024a https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-1075712 URI
024a https://doi.org/10.1124/dmd.109.0286542 DOI
024a https://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-189702 URI
040 a (SwePub)uud (SwePub)kth
041 a engb eng
042 9 SwePub
072 7a ref2 swepub-contenttype
072 7a art2 swepub-publicationtype
100a Ahlin, Gustav,d 1977-u Uppsala universitet,Institutionen för farmaci,Läkemedelsformulering4 aut0 (Swepub:uu)guahl109
2451 0a Endogenous Gene and Protein Expression of Drug Transporting Proteins in Cell Lines Routinely used in Drug Discovery Programs
264 c 2009-09-09
264 1b American Society for Pharmacology & Experimental Therapeutics (ASPET),c 2009
338 a print2 rdacarrier
500 a QC 20100525
520 a The aim of this study was to investigate the gene and protein expression profiles of important drug transporting proteins in human cell lines commonly used for studies of drug transport mechanisms. Human cell lines used to transiently or stably express single transporters (HeLa, HEK293) and leukaemia cell lines used to study drug resistance by ABC-transporters (HL-60, K562) were investigated, and compared with organotypic cell lines (HepG2, Saos-2, Caco-2 and Caco-2 TC7). For gene expression studies, real-time PCR was used, while monospecific polyclonal antibodies were generated and used to investigate protein expression by immunohistochemistry. Thirty-six transporters were studied for gene expression and nine for protein expression. The antibodies were validated using expression patterns in human tissues. Finally, the function of one ubiquitously expressed transporter, MCT1; SLC16A1 was investigated using 14C-lactic acid as a substrate. In general, the adherent cell lines (HeLa, HEK293) displayed low transporter expression and the expression patterns were barely affected by transfection. The leukaemia cell lines (K562, HL-60) and Saos-2 also had low endogenous transporter expression, while the organotypic cell lines (HepG2 and Caco-2) showed higher expression of some transporters. Comparison of gene and protein expression profiles gave poor correlations, but better agreement was obtained for antibodies with a good validation score, indicating that antibody quality was a significant variable. Importantly, the monocarboxylic acid transporting protein MCT1 was significantly expressed in all, and functional in most of the cell lines, indicating that MCT1 may be a confounding factor when the transport of small anionic drugs is investigated.
650 7a MEDICIN OCH HÄLSOVETENSKAPx Medicinska och farmaceutiska grundvetenskaperx Farmaceutiska vetenskaper0 (SwePub)301012 hsv//swe
650 7a MEDICAL AND HEALTH SCIENCESx Basic Medicinex Pharmaceutical Sciences0 (SwePub)301012 hsv//eng
653 a Cell lines
653 a Caco-2
653 a HEK293
653 a HeLa
653 a Saos-2
653 a HL-60
653 a K562
653 a HepG2
653 a Gene expression
653 a Protein expression
653 a MCT1
653 a PHARMACY
653 a FARMACI
653 a Biopharmaceutics
653 a Biofarmaci
653 a Galenisk farmaci
653 a Pharmaceutics
700a Hilgendorf, Constanzeu AstraZeneca R&D, Mölndal4 aut
700a Karlsson, Johanu AstraZeneca R&D, Mölndal, Sweden4 aut
700a Al-Khalili Szigyarto, Cristinau KTH,Proteomik,Department of Proteomics, The Royal Institute of Technology, Stockholm, Sweden4 aut0 (Swepub:kth)u1c02mh9
700a Uhlén, Mathiasu KTH,Proteomik,Department of Proteomics, The Royal Institute of Technology, Stockholm, Sweden4 aut0 (Swepub:kth)u1dulvmw
700a Artursson, Peru Uppsala universitet,Institutionen för farmaci4 aut0 (Swepub:uu)perartur
710a Uppsala universitetb Institutionen för farmaci4 org
773t Drug Metabolism And Dispositiond : American Society for Pharmacology & Experimental Therapeutics (ASPET)g 37:12, s. 2275-2283q 37:12<2275-2283x 0090-9556x 1521-009X
8564 8u https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-107571
8564 8u https://doi.org/10.1124/dmd.109.028654
8564 8u https://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-18970

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