Interferon-alpha-2b downregulation of oncogenes H-ras, c-raf-2, c-kit, c-myc, c-myb and c-fos in ESKOL, a hairy cell leukemic line, results in temporal perturbation of signal transduction cascade.
ESKOL, a B-lymphoblastoid cell line consisting of late differentiated cells, resembles hairy cell leukemia (HCL). It is pseudodiploid with a deleted 7q and an unbalanced translocation between chromosomes 4 and 6. It was screened by Northern hybridization for oncogenes, including H-ras, c-raf-2 (c-raf1p1), c-kit, c-myc, c-myb, c-fos, Fim-1, c-jun, ski, and c-mos, which are believed to contribute to B-cell differentiation and maturation. Interferon-alpha-2b (IFN) downregulates the expression of H-ras, c-raf-2, c-kit, c-myc, c-myb, c-fos, as determined by Northern hybridization of RNA isolated from cells harvested at time points during a 30 h time course. Downregulation of oncogenes H-ras, c-raf-2, c-kit, whose proteins are associated with cell surfaces or are cytosolar transducers, occurs before those oncogenes c-myc, c-myb, and c-fos, whose products are DNA binding proteins. This suggests a temporal perturbation of signal transduction by IFN. No change in oncogene expression occurred in non-treated cells nor were these oncogenes expressed in the non-transformed B-lymphoblast cell line, Wil-2, under the same treatment regimen. The basis for the IFN perturbation is not understood; yet the role of these oncogenes as signal transducers in differentiation and proliferation of human hematopoietic progenitors is unfolding, and ESKOL is an excellent system in which to study this phenomenon.
Harvey
W H
WH
Department of Biology, Earlham College, Richmond, IN 47374-4095.
Harb
O S
OS
Kosak
S T
ST
Sheaffer
J C
JC
Lowe
L R
LR
Heerema
N A
NA
D000368:Aged; D015152:Blotting, Northern; D015536:Down-Regulation; D015973:Gene Expression Regulation, Leukemic; D016762:Genes, fos / Q000235:genetics; D016259:Genes, myc / Q000235:genetics; D011905:Genes, ras / Q000235:genetics; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000494:pharmacology*; D007621:Karyotyping; D007943:Leukemia, Hairy Cell / Q000235:genetics* / Q000473:pathology; D008297:Male; D009693:Nucleic Acid Hybridization; D009857:Oncogenes / Q000235:genetics*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000235:genetics; D019009:Proto-Oncogene Proteins c-kit; D020598:Proto-Oncogene Proteins c-myb; D019908:Proto-Oncogene Proteins c-raf; D012334:RNA, Neoplasm / Q000032:analysis; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics; D016184:Receptors, Colony-Stimulating Factor / Q000235:genetics; D011994:Recombinant Proteins; D015398:Signal Transduction / Q000235:genetics*; D014407:Tumor Cells, Cultured
D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011518:Proto-Oncogene Proteins; D020598:Proto-Oncogene Proteins c-myb; D012334:RNA, Neoplasm; D016184:Receptors, Colony-Stimulating Factor; D011994:Recombinant Proteins; D019009:Proto-Oncogene Proteins c-kit; D020794:Receptor Protein-Tyrosine Kinases; D017346:Protein Serine-Threonine Kinases; D019908:Proto-Oncogene Proteins c-raf