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An oligomer complementary to c-myc mRNA inhibits proliferation of HL-60 promyelocytic cells and induces differentiation

Journal Article · · Mol. Cell. Biol.; (United States)
DOI:https://doi.org/10.1128/MCB.8.2.963· OSTI ID:5142711
To study the role of a nuclear proto-oncogene in the regulation of cell growth and differentiation, the authors inhibited HL-60 c-myc expression with a complementary antisense oligomer. This oligomer was stable in culture and entered cells, forming an intracellular duplex. Incubation of cells with the anti-myc oligomer decreased the steady-state levels of c-myc protein by 50 to 80%, whereas a control oligomer did not significantly affect the c-myc protein concentration. Direct inhibition of c-myc expression with the anti-myc oligomer was associated with a decreased cell growth rate and an induction of myeloid differentiation. Related antisense oligomers with 2- to 12-base-pair mismatches with c-myc RNA did not influence HL-60 cells. Thus, the effects of the antisense oligomer exhibited sequence specificity, and furthermore, these effects could be reversed by hybridization competition with another complementary oligomer. Antisense inhibition of a nuclear proto-oncogene apparently bypasses cell surface events in affecting cell proliferation and differentiation.
Research Organization:
Departments of Cell Biology and Pathology, Vanderbilt Univ. School of Medicine, Nashville, TN 37232 (US)
OSTI ID:
5142711
Journal Information:
Mol. Cell. Biol.; (United States), Journal Name: Mol. Cell. Biol.; (United States) Vol. 8:2; ISSN MCEBD
Country of Publication:
United States
Language:
English