The immediate early gene response to a differentiative stimulus is disrupted by the v-abl and v-ras oncogenes.
The immediate early gene activation in response to a differentiative stimulus was investigated in the hematopoietic progenitor cell line 32DC13(G). A transient and coordinated increase in mRNA levels for c-fos, c-jun, jun-B, TIS-7/PC-4, TIS-8/egr-1, and TIS-11 occurred during the first 2 h of treatment with granulocyte colony stimulating factor (G-CSF), which ultimately induces the 32DC13(G) cells to terminally differentiate into neutrophilic granulocytes. This pattern of mRNA induction was disrupted by v-abl and v-ras, two oncogenes known to interfere with G-CSF-induced differentiation of 32DC13(G) cells. Induction of the mRNAs for c-jun and TIS-7/PC-4 was blocked by the presence of v-abl, whereas v-ras caused constitutive expression of c-fos mRNA and blocked the c-jun, jun-B and TIS-7/PC-4 mRNA response. Release of the differentiation block in the ras-transformed 32DC13(G) cells by co-treatment with retinoic acid and G-CSF partially restored the normal c-fos and c-jun mRNA induction pattern, suggesting that the proper activation of these genes may be important for myeloid differentiation.
Wistar Institute of Anatomy and Biology, Philadelphia, Pennsylvania 19104.
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BL
Kreider
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Rovera
D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics; D002478:Cells, Cultured; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics*; D016313:Genes, abl / Q000502:physiology*; D016762:Genes, fos; D016758:Genes, jun; D011905:Genes, ras / Q000502:physiology*; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism*; D014158:Transcription, Genetic / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D015533:Transcriptional Activation; D014212:Tretinoin / Q000494:pharmacology
D012333:RNA, Messenger; D016179:Granulocyte Colony-Stimulating Factor; D014212:Tretinoin