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.
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.
authors.affiliation: CRC Experimental Haematology Group, Paterson Institute for Cancer Research, Christie Hospital NHS Trust, Manchester, UK.
authors.forename: C M
authors.initials: CM
authors.lastname: Heyworth
authors.forename: D
authors.initials: D
authors.lastname: Gagen
authors.forename: K G
authors.initials: KG
authors.lastname: Edington
authors.forename: L J
authors.initials: LJ
authors.lastname: Fairbairn
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000096:biosynthesis / Q000502:physiology*; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002454:Cell Differentiation; D002455:Cell Division; D002999:Clone Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D017077:Culture Media, Conditioned / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm; D005047:Etoposide / Q000494:pharmacology; D005456:Fluorescent Dyes / Q000378:metabolism; D019450:Genes, MDR; D016298:Hematopoietic Cell Growth Factors / Q000494:pharmacology; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D051379:Mice; D010446:Peptide Fragments / Q000378:metabolism; D017475:Receptors, Nerve Growth Factor / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000502:physiology; D012235:Rhodamines / Q000378:metabolism; D014162:Transfection; D014700:Verapamil / Q000494:pharmacology
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000970:Antineoplastic Agents; D002121:Calcium Channel Blockers; D017077:Culture Media, Conditioned; D005456:Fluorescent Dyes; D016298:Hematopoietic Cell Growth Factors; D010446:Peptide Fragments; D017475:Receptors, Nerve Growth Factor; D011993:Recombinant Fusion Proteins; D012235:Rhodamines; D005047:Etoposide; D014700:Verapamil