Tumour-specific inhibition of lymphoma growth by an antisense oligodeoxynucleotide.
In a high proportion of Burkitt lymphomas, transcription of the c-myc gene is initiated from a cryptic promoter in the first intron, creating abnormal messenger RNA molecules in which intron sequences, normally spliced out of the nascent transcripts, persist. An antisense oligodeoxynucleotide directed against these intron sequences greatly inhibited the proliferation of Burkitt lymphoma cell lines containing the abnormal transcripts (ST486 and JD38), but not that of cell lines containing normal c-myc transcripts (KK124). Flow cytometry showed a pronounced reduction in intracellular c-myc protein levels in cell lines containing aberrant myc transcripts, but no change in other cellular proteins. Control oligonucleotide did not inhibit c-myc protein expression or growth. These experiments provide evidence that antisense oligonucleotides targeted against tumour-specific, aberrant RNA species could be effective in controlling the proliferation of tumour cells without affecting normal cells.
McManaway
M E
ME
Pediatric Branch, National Cancer Institute, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892.
Neckers
L M
LM
Loke
S L
SL
al-Nasser
A A
AA
Redner
R L
RL
Shiramizu
B T
BT
Goldschmidts
W L
WL
Huber
B E
BE
Bhatia
K
K
Magrath
I T
IT
D001483:Base Sequence; D002051:Burkitt Lymphoma / Q000235:genetics / Q000473:pathology*; D002455:Cell Division / Q000187:drug effects; D004273:DNA, Neoplasm / Q000187:drug effects* / Q000235:genetics; D004353:Drug Evaluation, Preclinical; D006801:Humans; D007438:Introns / Q000187:drug effects*; D008969:Molecular Sequence Data; D009841:Oligonucleotides / Q000032:analysis / Q000494:pharmacology*; D016376:Oligonucleotides, Antisense; D009857:Oncogenes; D011518:Proto-Oncogene Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics; D016271:Proto-Oncogene Proteins c-myc; D013997:Time Factors
D004273:DNA, Neoplasm; D009841:Oligonucleotides; D016376:Oligonucleotides, Antisense; D011518:Proto-Oncogene Proteins; D016271:Proto-Oncogene Proteins c-myc