Retroviral transfer and expression of human MDR-1 in a murine haemopoietic stem cell line does not alter factor dependence, growth or differentiation characteristics.

2.50
Hdl Handle:
http://hdl.handle.net/10541/82439
Title:
Retroviral transfer and expression of human MDR-1 in a murine haemopoietic stem cell line does not alter factor dependence, growth or differentiation characteristics.
Authors:
Heyworth, Clare M; Gagen, D; Edington, Kirsten G; Fairbairn, Leslie J
Abstract:
In view of the recent report of a myeloproliferative syndrome in mice that had received an MDR-1-transduced haemopoietic graft, we have investigated the potential effects of MDR-1 expression on primitive haemopoietic cell growth and differentiation. Retroviral gene transfer was used to achieve exogenous expression of either MDR-1 or truncated nerve growth factor receptor (tNGFR) in the multipotent murine haemopoietic progenitor cell line, FDCP-mix. Following gene transfer, clonal lines were derived and FACS analysis confirmed appropriate expression of each transgene. MDR-1 (but not tNGFR) expression was associated with verapamil-sensitive rhodamine efflux and resistance to killing by etoposide. When growth factor responsiveness, proliferative capacity and differentiation capacity were examined, MDR-1 expressing FDCP-mix cells exhibited a normal phenotype and mimicked the response of tNGFR-expressing or untransduced FDCP-mix cells. Thus, in the model system we have used, MDR-1 does not perturb haemopoietic cell growth and development and our data do not support a myeloproliferative role for MDR-1.
Affiliation:
CRC Experimental Haematology Group, Paterson Institute for Cancer Research, Christie Hospital NHS Trust, Manchester, UK.
Citation:
Retroviral transfer and expression of human MDR-1 in a murine haemopoietic stem cell line does not alter factor dependence, growth or differentiation characteristics. 2002, 16 (1):106-11 Leukemia
Journal:
Leukemia
Issue Date:
Jan-2002
URI:
http://hdl.handle.net/10541/82439
DOI:
10.1038/sj.leu.2402333
PubMed ID:
11840269
Type:
Article
Language:
en
ISSN:
0887-6924
Appears in Collections:
All Paterson Institute for Cancer Research

Full metadata record

DC FieldValue Language
dc.contributor.authorHeyworth, Clare M-
dc.contributor.authorGagen, D-
dc.contributor.authorEdington, Kirsten G-
dc.contributor.authorFairbairn, Leslie J-
dc.date.accessioned2009-09-24T09:25:35Z-
dc.date.available2009-09-24T09:25:35Z-
dc.date.issued2002-01-
dc.identifier.citationRetroviral transfer and expression of human MDR-1 in a murine haemopoietic stem cell line does not alter factor dependence, growth or differentiation characteristics. 2002, 16 (1):106-11 Leukemiaen
dc.identifier.issn0887-6924-
dc.identifier.pmid11840269-
dc.identifier.doi10.1038/sj.leu.2402333-
dc.identifier.urihttp://hdl.handle.net/10541/82439-
dc.description.abstractIn view of the recent report of a myeloproliferative syndrome in mice that had received an MDR-1-transduced haemopoietic graft, we have investigated the potential effects of MDR-1 expression on primitive haemopoietic cell growth and differentiation. Retroviral gene transfer was used to achieve exogenous expression of either MDR-1 or truncated nerve growth factor receptor (tNGFR) in the multipotent murine haemopoietic progenitor cell line, FDCP-mix. Following gene transfer, clonal lines were derived and FACS analysis confirmed appropriate expression of each transgene. MDR-1 (but not tNGFR) expression was associated with verapamil-sensitive rhodamine efflux and resistance to killing by etoposide. When growth factor responsiveness, proliferative capacity and differentiation capacity were examined, MDR-1 expressing FDCP-mix cells exhibited a normal phenotype and mimicked the response of tNGFR-expressing or untransduced FDCP-mix cells. Thus, in the model system we have used, MDR-1 does not perturb haemopoietic cell growth and development and our data do not support a myeloproliferative role for MDR-1.en
dc.language.isoenen
dc.subjectHaematopoietic Stem Cellsen
dc.subjectHaematopoietic Cell Growth Factorsen
dc.subject.meshAnimals-
dc.subject.meshAntineoplastic Agents-
dc.subject.meshCalcium Channel Blockers-
dc.subject.meshCell Differentiation-
dc.subject.meshCell Division-
dc.subject.meshClone Cells-
dc.subject.meshCulture Media, Conditioned-
dc.subject.meshDrug Resistance, Neoplasm-
dc.subject.meshEtoposide-
dc.subject.meshFluorescent Dyes-
dc.subject.meshGenes, MDR-
dc.subject.meshHematopoietic Cell Growth Factors-
dc.subject.meshHematopoietic Stem Cells-
dc.subject.meshHumans-
dc.subject.meshMice-
dc.subject.meshP-Glycoprotein-
dc.subject.meshPeptide Fragments-
dc.subject.meshReceptors, Nerve Growth Factor-
dc.subject.meshRecombinant Fusion Proteins-
dc.subject.meshRhodamines-
dc.subject.meshTransfection-
dc.subject.meshVerapamil-
dc.titleRetroviral transfer and expression of human MDR-1 in a murine haemopoietic stem cell line does not alter factor dependence, growth or differentiation characteristics.en
dc.typeArticleen
dc.contributor.departmentCRC Experimental Haematology Group, Paterson Institute for Cancer Research, Christie Hospital NHS Trust, Manchester, UK.en
dc.identifier.journalLeukemiaen

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