Interferon induces up-regulation of Spi-1/PU.1 in human leukemia K562 cells.
The human K562 cell line is derived from a chronic myelogenous leukemia in blastic crisis. Treatment of K562 cells with interferons alpha, beta or gamma resulted in inhibition of cell proliferation. Spi-1/PU.1 is a transcription factor of the Ets family which is required for normal hematopoyesis. We have found that spi-1 mRNA and protein as well as Spi-1-DNA binding activity increase after exposure of K562 cells to interferons. The increase in spi-1 expression ranged from 4- to 8-fold with the different interferons. K562 cells can be differentiated in vitro towards erythroid cells or monocyte-macrophage cells. Interestingly, the regulation of spi-1 by interferon-alpha depended on the differentiated phenotype of K562 cells: interferon-alpha failed to induce spi-1 in erythroid differentiated cells, whereas it induced spi-1 in monocyte-macrophage differentiated cells. The results suggest a role for Spi-1 in the cytostatic response to interferons.
Gutiérrez
P
P
Departamento de Biología Molecular, Universidad de Cantabria, Santander, Spain.
Delgado
M D
MD
Richard
C
C
Moreau-Gachelin
F
F
León
J
J
D000818:Animals; D001752:Blast Crisis; D015152:Blotting, Northern; D015153:Blotting, Western; D019556:COS Cells; D002454:Cell Differentiation; D002455:Cell Division; D004273:DNA, Neoplasm / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006410:Hematopoiesis; D006801:Humans; D007372:Interferons / Q000494:pharmacology*; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D009687:Nuclear Proteins / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D015534:Trans-Activators / Q000235:genetics* / Q000378:metabolism; D014162:Transfection; D014407:Tumor Cells, Cultured; D015854:Up-Regulation; D000099232:Proto-Oncogene Protein Spi-1
D004273:DNA, Neoplasm; D007372:Interferons; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D015534:Trans-Activators; D000099232:Proto-Oncogene Protein Spi-1