Suppression of c-myc oncogene expression by a polyamine-complexed triplex forming oligonucleotide in MCF-7 breast cancer cells

T. J. Thomas, Carol A. Faaland, Michael A. Gallo, Thresla Thomas

Research output: Contribution to journalArticle

54 Citations (Scopus)

Abstract

Polyamines are excellent stabilizers of triplex DNA. Recent studies in our laboratory revealed a remarkable structural specificity of polyamines in the induction and stabilization of triplex DNA. 1,3-Diaminopropane (DAP) showed optimum efficacy amongst a series of synthetic diamines in stabilizing triplex DNA. To utilize the potential of this finding in developing an anti-gene strategy for breast cancer, we treated MCF-7 cells with a 37mer oligonucleotide to form triplex DNA in the up-stream regulatory region of the c-myc oncogene in the presence of DAP. As individual agents, the oligonucleotide and DAP did not downregulate c-myc mRNA in the presence of estradiol. Complexation of the oligonucleotide with 2 mM DAP reduced c-myc mRNA signal by 65% at 10 μM oligonucleotide concentration. In contrast, a control oligonucleotide had no significant effect on c-myc mRNA. The expression ofc-fos oncogene was not significantly altered by the triplex forming oligonucleotide (TFO). DAP was internalized within 1 h of treatment; however, it had no significant effect on the level of natural polyamines. These data indicate that selective utilization of synthetic polyamines and TFOs might be an important strategy to develop anti-gene-based therapeutic modalities for breast cancer.

Original languageEnglish (US)
Pages (from-to)3594-3599
Number of pages6
JournalNucleic acids research
Volume23
Issue number17
DOIs
StatePublished - Sep 11 1995

Fingerprint

myc Genes
Polyamines
Oligonucleotides
Breast Neoplasms
Messenger RNA
Diamines
Nucleic Acid Regulatory Sequences
MCF-7 Cells
Oncogenes
Genes
Estradiol
Down-Regulation
trimethylenediamine
triplex DNA

All Science Journal Classification (ASJC) codes

  • Genetics

Cite this

Thomas, T. J. ; Faaland, Carol A. ; Gallo, Michael A. ; Thomas, Thresla. / Suppression of c-myc oncogene expression by a polyamine-complexed triplex forming oligonucleotide in MCF-7 breast cancer cells. In: Nucleic acids research. 1995 ; Vol. 23, No. 17. pp. 3594-3599.
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Suppression of c-myc oncogene expression by a polyamine-complexed triplex forming oligonucleotide in MCF-7 breast cancer cells. / Thomas, T. J.; Faaland, Carol A.; Gallo, Michael A.; Thomas, Thresla.

In: Nucleic acids research, Vol. 23, No. 17, 11.09.1995, p. 3594-3599.

Research output: Contribution to journalArticle

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