Sökning: WFRF:(Al Khalili Szigyarto Cristina) > Endogenous Gene and...
Fältnamn | Indikatorer | Metadata |
---|---|---|
000 | 04508naa a2200601 4500 | |
001 | oai:DiVA.org:uu-107571 | |
003 | SwePub | |
008 | 090817s2009 | |||||||||||000 ||eng| | |
009 | oai:DiVA.org:kth-18970 | |
024 | 7 | a https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-1075712 URI |
024 | 7 | a https://doi.org/10.1124/dmd.109.0286542 DOI |
024 | 7 | a 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 | 7 | a ref2 swepub-contenttype |
072 | 7 | a art2 swepub-publicationtype |
100 | 1 | a Ahlin, Gustav,d 1977-u Uppsala universitet,Institutionen för farmaci,Läkemedelsformulering4 aut0 (Swepub:uu)guahl109 |
245 | 1 0 | a Endogenous Gene and Protein Expression of Drug Transporting Proteins in Cell Lines Routinely used in Drug Discovery Programs |
264 | c 2009-09-09 | |
264 | 1 | b 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 | 7 | a MEDICIN OCH HÄLSOVETENSKAPx Medicinska och farmaceutiska grundvetenskaperx Farmaceutiska vetenskaper0 (SwePub)301012 hsv//swe |
650 | 7 | a 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 | |
700 | 1 | a Hilgendorf, Constanzeu AstraZeneca R&D, Mölndal4 aut |
700 | 1 | a Karlsson, Johanu AstraZeneca R&D, Mölndal, Sweden4 aut |
700 | 1 | a Al-Khalili Szigyarto, Cristinau KTH,Proteomik,Department of Proteomics, The Royal Institute of Technology, Stockholm, Sweden4 aut0 (Swepub:kth)u1c02mh9 |
700 | 1 | a Uhlén, Mathiasu KTH,Proteomik,Department of Proteomics, The Royal Institute of Technology, Stockholm, Sweden4 aut0 (Swepub:kth)u1dulvmw |
700 | 1 | a Artursson, Peru Uppsala universitet,Institutionen för farmaci4 aut0 (Swepub:uu)perartur |
710 | 2 | a Uppsala universitetb Institutionen för farmaci4 org |
773 | 0 | t 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 |
856 | 4 8 | u https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-107571 |
856 | 4 8 | u https://doi.org/10.1124/dmd.109.028654 |
856 | 4 8 | u https://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-18970 |
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