Transcriptional control of the endogenous MYC protooncogene by antisense RNA.

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Abstract
A plasmid carrying antisense human MYC DNA And the gene encoding Escherichia coli xanthine/guanine phosporibosyltransferase (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 > 6 months. The constitutive production of MYC protein 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.