{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T15:42:36Z","timestamp":1790869356035,"version":"4.1.0"},"reference-count":6,"publisher":"S. Karger AG","issue":"4","license":[{"start":{"date-parts":[[1999,1,1]],"date-time":"1999-01-01T00:00:00Z","timestamp":915148800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.karger.com\/Services\/SiteLicenses"},{"start":{"date-parts":[[1999,1,1]],"date-time":"1999-01-01T00:00:00Z","timestamp":915148800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.karger.com\/Services\/SiteLicenses"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Horm Res Paediatr"],"published-print":{"date-parts":[[1999]]},"abstract":"<jats:p>The debate about a direct or indirect effect of GH and IGF-I on the recurrence of malignancy, especially in the case of rhGH therapy in patients with leukemia, is still going on. Recent studies suggested that IGF-I plays a role in drug resistance during anticancer therapy. This resistance to diverse cytotoxic drugs, named multidrug-resistance (MDR), is mainly due to high levels of P-glycoprotein (P-gp). The gene encoding this membrane-associated transporter protein was named MDR1, and increased levels of P-gp are linked to enhanced MDR1 mRNA expression. Our aim was to investigate a possible effect of rhIGF-I on MDR1 gene expression in vitro. We cultured the T-lymphoblastoid cell line CCRF-CEM with different rhIGF-I concentrations (0, 5, 20 and 50 ng\/ml) in serum-free medium for 3 days. CCRF-CEM cells are drug-sensitive and express MDR1 at low levels. MDR1 mRNA expression was measured by semiquantitative RT-PCR using a competitive assay with a heterologous DNA construct. In addition, GAPDH mRNA was amplified as an internal control for RNA integrity. P-gp activity was determined by a flow cytometric assay measuring rhodamine 123 accumulation. Furthermore, cell proliferation was monitored in all experiments. Our data do not support an effect of rhIGF-I on MDR1 mRNA expression, P-gp activity or cell proliferation in the CCRF-CEM cell line. MDR1 mRNA levels were inversely correlated to cell density with high significance (p &lt; 0.0001). In conclusion, multidrug resistance linked to P-gp is not induced by IGF-I in CCRF-CEM cells. At high density, CCRF-CEM cells downregulate MDR1 gene expression. Our experimental model provides a very useful tool for monitoring the influence of growth factors on multidrug resistance in vitro.<\/jats:p>","DOI":"10.1159\/000023460","type":"journal-article","created":{"date-parts":[[2003,4,15]],"date-time":"2003-04-15T10:10:37Z","timestamp":1050401437000},"page":"192-199","source":"Crossref","is-referenced-by-count":1,"title":["Influence of IGF-I and Cell Density on MDR1 Expression in the T-Lymphoblastoid Cell Line CCRF-CEM"],"prefix":"10.1159","volume":"52","author":[{"given":"C.P.","family":"Schwarze","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.","family":"Neu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.","family":"Beck","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K.","family":"Mavridou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.B.","family":"Ranke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G.","family":"Binder","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"127","published-online":{"date-parts":[[2000,3,9]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-4652(199805)175:2<141::AID-JCP3>3.0.CO;2-O"},{"key":"ref2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.physiol.47.1.425"},{"key":"ref3","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.1995.2450"},{"key":"ref4","doi-asserted-by":"publisher","DOI":"10.1038\/359557a0"},{"key":"ref5","doi-asserted-by":"publisher","DOI":"10.1006\/excr.1994.1329"},{"key":"ref6","doi-asserted-by":"publisher","DOI":"10.1016\/0303-7207(94)90025-6"}],"container-title":["Hormone Research in Paediatrics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.karger.com\/Article\/Pdf\/23460","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.karger.com\/Article\/Pdf\/23460","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,24]],"date-time":"2025-04-24T04:51:15Z","timestamp":1745470275000},"score":1,"resource":{"primary":{"URL":"https:\/\/karger.com\/article\/doi\/10.1159\/000023460"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1999]]},"references-count":6,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2000,3,1]]}},"URL":"https:\/\/doi.org\/10.1159\/000023460","archive":["Portico"],"relation":{},"ISSN":["1663-2818","1663-2826"],"issn-type":[{"value":"1663-2818","type":"print"},{"value":"1663-2826","type":"electronic"}],"subject":[],"published":{"date-parts":[[1999]]}}}