TY - JOUR
T1 - 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
AU - Harvey, William H.
AU - Harb, Omar S.
AU - Kosak, Steven T.
AU - Sheaffer, J. Christian
AU - Lowe, Lisa R.
AU - Heerema, Nyla A.
N1 - Funding Information:
Acknowledgements--This work was supported by the Howard Hughes Medical Institute in a grant to Earlham College. Shirley Rodgers, Adrienne Shields, Nancy Parker, David Jeffries, Terry Mays and Rebecca Dyer provided support in the lab for which the authors are most appreciative.
PY - 1994/8
Y1 - 1994/8
N2 - 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-rafp1), 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.
AB - 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-rafp1), 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.
KW - B-cell differentiation
KW - H-ras
KW - Interferon
KW - c-fos
KW - c-kit
KW - c-myb
KW - c-myc
KW - c-raf-2
KW - downregulation
KW - hairy cell leukemia
KW - oncogenes
KW - signal transduction
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U2 - 10.1016/0145-2126(94)90039-6
DO - 10.1016/0145-2126(94)90039-6
M3 - Article
C2 - 7520517
AN - SCOPUS:0027983593
SN - 0145-2126
VL - 18
SP - 577
EP - 585
JO - Leukemia Research
JF - Leukemia Research
IS - 8
ER -