Recombinant tumor necrosis factor alpha and interleukin 1 alpha increase expression of c-abl protooncogene mRNA in cultured human marrow stromal cells.
Analysis of protooncogene RNA expression in marrow stromal cells from long-term marrow culture demonstrated high levels of c-abl 5-, 6-, and 7-kilobase (kb) RNA transcripts. In experiments on three independently derived simian virus 40-transformed marrow stromal cell lines, the expression of these c-abl transcripts was further increased in response to recombinant tumor necrosis factor alpha (1000 units/ml) and interleukin 1 alpha (10 units/ml). Although lymphocyte-conditioned medium predominantly up-regulated the 5-kb transcript, interleukin 1 alpha primarily affected the 6-kb transcript. The up-regulation of the 5-kb c-abl message correlated with up-regulation of the granulocyte/macrophage colony-stimulating factor transcript and down-regulation of procollagen I transcripts in transformed cells. These data suggest that c-abl plays roles in the regulation of extracellular matrix expression and in the regulation of hematopoietic growth factors by stromal cells.
Andrews
D F
DF
Department of Medicine, University of Washington, Fred Hutchinson Cancer Research Center, Seattle.
Nemunaitis
J J
JJ
Singer
J W
JW
D015152:Blotting, Northern; D001853:Bone Marrow / Q000187:drug effects / Q000378:metabolism*; D001854:Bone Marrow Cells; D002478:Cells, Cultured; D003115:Colony-Stimulating Factors / Q000235:genetics; D005796:Genes / Q000187:drug effects; D011905:Genes, ras / Q000187:drug effects; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D006133:Growth Substances / Q000235:genetics; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology*; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D016315:Proto-Oncogene Proteins c-abl; D011519:Proto-Oncogenes / Q000187:drug effects*; D012333:RNA, Messenger / Q000235:genetics*; D011994:Recombinant Proteins / Q000494:pharmacology; D014158:Transcription, Genetic / Q000187:drug effects*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D003115:Colony-Stimulating Factors; D006133:Growth Substances; D007375:Interleukin-1; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D016315:Proto-Oncogene Proteins c-abl