Anthracycline-induced erythroid differentiation of K562 cells is inhibited by p28, a novel mammalian glutathione-binding stress protein.
When exposed to the anthracycline doxorubicin, K562 cells undergo differentiation which is characterized by arrested cell division, an increased mean cell diameter, and the production of hemoglobin. The influence of expression of p28, a low-molecular weight stress protein, on the differentiation of K562 cells was examined. Expression of p28 was modulated by transfection of K562 cells with expression vectors containing the murine p28 cDNA in either the sense or antisense orientation, or without the p28 cDNA. In K562 cells where p28 expression was either unaltered or downregulated, exposure to 40 nM Doxorubicin resulted in an arrest of cell division, the production of hemoglobin, and an increased cell diameter consistent with cells undergoing differentiation. K562 cells that overexpressed p28 continued to divide, had fewer hemoglobin-producing cells, had a smaller mean cell diameter and had a 5.5-fold increase in cell survival. Consistent with an inhibition of doxorubicin-induced erythroid differentiation, p28 may act by changes in redox regulation via the glutathione-binding activity of p28 and suggests a general role for p28 in cellular differentiation. Furthermore, p28 expression may be useful in predicting resistance to chemo- or radiation therapy in the treatment of leukemia and lymphoma.
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Department of Experimental Radiation Biology, Box 66, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX 77030, USA.
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D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D015415:Biomarkers; D015152:Blotting, Northern; D002352:Carrier Proteins / Q000235:genetics / Q000502:physiology*; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology*; D004317:Doxorubicin / Q000494:pharmacology*; D005982:Glutathione Transferase; D006801:Humans; D020014:K562 Cells; D012333:RNA, Messenger / Q000235:genetics
D000903:Antibiotics, Antineoplastic; D015415:Biomarkers; D002352:Carrier Proteins; C117709:Gsto1 protein, mouse; D012333:RNA, Messenger; D004317:Doxorubicin; D005982:Glutathione Transferase