Overexpression of murine WT1 + / + and - / - isoforms has no effect on chemoresistance but delays differentiation in the K562 leukemia cell line.
The Wilms' tumor gene (WT1) encodes a zinc-finger transcription factor that is expressed as four distinct isoforms designated as, + / +, + / -, - / + and - / -. It is expressed in leukemic cells, and is proposed to play a role in their proliferation and differentiation. In this study we have shown that cell lines of the erythroleukemia, K562, overexpressing the murine + / + and - / - WT1 isoforms grow normally and do not exhibit altered responses to the induction of apoptosis by the reagents cisplatin and adriamycin, or to serum withdrawal. However, differentiation of K562 cells with 12-O-tetradecanoylphorbol 13-acetate, modeling aspects of megakaryopoiesis, was partially inhibited by the persistent expression of both the murine + / + and - / - WT1 isoforms. This finding suggests that WT1 plays a role in the regulation of hematopoietic differentiation and is consistent with an oncogenic role for WT1 in leukemogenesis.
Carrington
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Department of Haematology and Oncology, Royal Children's Hospital, Parkville, Australia.
Algar
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E
D000818:Animals; D000970:Antineoplastic Agents / Q000633:toxicity*; D017209:Apoptosis / Q000187:drug effects; D002454:Cell Differentiation; D002455:Cell Division / Q000187:drug effects; D002945:Cisplatin / Q000633:toxicity*; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D004317:Doxorubicin / Q000633:toxicity*; D018432:Drug Resistance, Multiple; D016162:Genes, Wilms Tumor; D006410:Hematopoiesis / Q000502:physiology; D006801:Humans; D020014:K562 Cells; D008533:Megakaryocytes / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D051379:Mice; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D014162:Transfection; D025721:WT1 Proteins
D000970:Antineoplastic Agents; D004268:DNA-Binding Proteins; D020033:Protein Isoforms; D011994:Recombinant Proteins; D014157:Transcription Factors; D025721:WT1 Proteins; D004317:Doxorubicin; D013755:Tetradecanoylphorbol Acetate; D002945:Cisplatin