Sökning: WFRF:(Al Khalili Szigyarto Cristina) >
Endogenous Gene and...
-
Ahlin, Gustav,1977-Uppsala universitet,Institutionen för farmaci,Läkemedelsformulering
(författare)
Endogenous Gene and Protein Expression of Drug Transporting Proteins in Cell Lines Routinely used in Drug Discovery Programs
- Artikel/kapitelEngelska2009
Förlag, utgivningsår, omfång ...
-
2009-09-09
-
American Society for Pharmacology & Experimental Therapeutics (ASPET),2009
-
printrdacarrier
Nummerbeteckningar
-
LIBRIS-ID:oai:DiVA.org:uu-107571
-
https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-107571URI
-
https://doi.org/10.1124/dmd.109.028654DOI
-
https://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-18970URI
Kompletterande språkuppgifter
-
Språk:engelska
-
Sammanfattning på:engelska
Ingår i deldatabas
Klassifikation
-
Ämneskategori:ref swepub-contenttype
-
Ämneskategori:art swepub-publicationtype
Anmärkningar
-
QC 20100525
-
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.
Ämnesord och genrebeteckningar
Biuppslag (personer, institutioner, konferenser, titlar ...)
-
Hilgendorf, ConstanzeAstraZeneca R&D, Mölndal
(författare)
-
Karlsson, JohanAstraZeneca R&D, Mölndal, Sweden
(författare)
-
Al-Khalili Szigyarto, CristinaKTH,Proteomik,Department of Proteomics, The Royal Institute of Technology, Stockholm, Sweden(Swepub:kth)u1c02mh9
(författare)
-
Uhlén, MathiasKTH,Proteomik,Department of Proteomics, The Royal Institute of Technology, Stockholm, Sweden(Swepub:kth)u1dulvmw
(författare)
-
Artursson, PerUppsala universitet,Institutionen för farmaci(Swepub:uu)perartur
(författare)
-
Uppsala universitetInstitutionen för farmaci
(creator_code:org_t)
Sammanhörande titlar
-
Ingår i:Drug Metabolism And Disposition: American Society for Pharmacology & Experimental Therapeutics (ASPET)37:12, s. 2275-22830090-95561521-009X
Internetlänk
Hitta via bibliotek
Till lärosätets databas