DOI: 10.1073/pnas.94.2.684. Inhibition of tumorigenesis by a cytosine–DNA, methyltransferase, antisense oligodeoxynucleotide

Inhibition of tumorigenesis by a cytosine–DNA, methyltransferase, antisense oligodeoxynucleotide

10.1073/pnas.94.2.684

Crossref journal-article

Proceedings of the National Academy of Sciences

Proceedings of the National Academy of Sciences (341)

Abstract

This paper tests the hypothesis that cytosine DNA methyltransferase (DNA MeTase) is a candidate target for anticancer therapy. Several observations have suggested recently that hyperactivation of DNA MeTase plays a critical role in initiation and progression of cancer and that its up-regulation is a component of the Ras oncogenic signaling pathway. We show that a phosphorothioate-modified, antisense oligodeoxynucleotide directed against the DNA MeTase mRNA reduces the level of DNA MeTase mRNA, inhibits DNA MeTase activity, and inhibits anchorage independent growth of Y1 adrenocortical carcinoma cells ex vivo in a dose-dependent manner. Injection of DNA MeTase antisense oligodeoxynucleotides i.p. inhibits the growth of Y1 tumors in syngeneic LAF1 mice, reduces the level of DNA MeTase, and induces demethylation of the adrenocortical-specific gene C21 and its expression in tumors in vivo . These results support the hypothesis that an increase in DNA MeTase activity is critical for tumorigenesis and is reversible by pharmacological inhibition of DNA MeTase.

Bibliography

Ramchandani, S., MacLeod, A. R., Pinard, M., von Hofe, E., & Szyf, M. (1997). Inhibition of tumorigenesis by a cytosineâDNA, methyltransferase, antisenseâoligodeoxynucleotide. Proceedings of the National Academy of Sciences, 94(2), 684â689.

Authors 5

Shyam Ramchandani (first)
A. Robert MacLeod (additional)
Marc Pinard (additional)
Eric von Hofe (additional)
Moshe Szyf (additional)

References 55 Referenced 138

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Dates

Type	When
Created	23 years, 1 month ago (July 26, 2002, 10:40 a.m.)
Deposited	3 years, 4 months ago (April 13, 2022, 3:14 p.m.)
Indexed	1 month ago (Aug. 2, 2025, 12:36 a.m.)
Issued	28 years, 7 months ago (Jan. 21, 1997)
Published	28 years, 7 months ago (Jan. 21, 1997)
Published Online	28 years, 7 months ago (Jan. 21, 1997)
Published Print	28 years, 7 months ago (Jan. 21, 1997)

Funders 0

None

BibTeX

@article{Ramchandani_1997, title={Inhibition of tumorigenesis by a cytosine–DNA, methyltransferase, antisense oligodeoxynucleotide}, volume={94}, ISSN={1091-6490}, url={http://dx.doi.org/10.1073/pnas.94.2.684}, DOI={10.1073/pnas.94.2.684}, number={2}, journal={Proceedings of the National Academy of Sciences}, publisher={Proceedings of the National Academy of Sciences}, author={Ramchandani, Shyam and MacLeod, A. Robert and Pinard, Marc and von Hofe, Eric and Szyf, Moshe}, year={1997}, month=jan, pages={684–689} }

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      "group": {
        "name": "publication_history",
        "label": "Publication History"
      }
    }
  ]
}