Transcriptional control of the endogenous MYC protooncogene by antisense RNA.

K Yokoyama, F Imamoto - Proceedings of the National …, 1987 - National Acad Sciences
K Yokoyama, F Imamoto
Proceedings of the National Academy of Sciences, 1987National Acad Sciences
A plasmid carrying antisense human MYC DNA and the gene encoding Escherichia coli
xanthine/guanine phosphoribosyltransferase (Ecogpt) was introduced into human
promyelocytic leukemia cell line HL-60 by protoplast fusion. High-level expression of
antisense MYC RNA was obtained by selecting cells resistant to progressively higher levels
of mycophenolic acid over a period of greater than 6 months. The constitutive production of
MYC protein in clones producing high levels of antisense MYC RNA was reduced by 70 …
A plasmid carrying antisense human MYC DNA and the gene encoding Escherichia coli xanthine/guanine phosphoribosyltransferase (Ecogpt) was introduced into human promyelocytic leukemia cell line HL-60 by protoplast fusion. High-level expression of antisense MYC RNA was obtained by selecting cells resistant to progressively higher levels of mycophenolic acid over a period of greater than 6 months. The constitutive production of MYC protein in clones producing high levels of antisense MYC RNA was reduced by 70% compared to parental HL-60 cells. Inhibition of MYC expression was observed not only at the translational but also at the transcriptional level, implying that antisense RNA can regulate transcription of the MYC gene. The Pst I-Pvu II fragment (920 base pairs) of the MYC leader sequence is the primary transcriptional target of the antisense RNA. The suppression of endogenous MYC gene expression by antisense RNA decreases cell proliferation and triggers monocytic differentiation.
National Acad Sciences