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Posttranscriptional regulation of c-myc proto-oncogene expression and growth inhibition by recombinant human interferon-β ser17 in a human colon carcinoma cell line

  • Original Articles
  • Proto-Oncogene, Colon Carcinoma Cell Line, Interferon-β
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Summary

Recombinant human interferon-β ser17 (IFN-β ser17), a cytokine that exhibits both antiviral and antiproliferative activity against a wide variety of cell types, causes a time- and dose-dependent inhibition of monolayer growth and of the expression of the c-myc proto-oncogene in DLD-l Clone A human colon-carcinoma cells. The suppression of c-myc expression mediated by IFN-β ser17 is due to a posttranscriptional destabilization of c-myc mRNA rather than to an inhibition of c-myc mRNA transcription. There is evidence suggesting that the selective reduction in the half-life of c-myc mRNA in IFN-β ser17-treated cells occurs through an increase in the activity of the 2′,5′-oligoadenylate synthetase/RNase L [2′,5′-oligo (A) synthetase] pathway in DLD-1 Clone A cells. Cotreatment of these cells with IFN-β ser17 and the anticancer agentN-methylformamide leads to the partial abrogation of 2′,5′-oligo (A) synthetase activity and the stabilization of c-myc mRNA. These findings suggest that there is a correlation between the IFN-β ser17-mediated suppression of c-myc expression and the induction of 2′,5′-oligo (A) synthetase activity in DLD-1 clone A cells.

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  1. Division of Biology and Medicine, Section of Molecular and Biochemical Pharmacology, Brown University, Box G B418, 02912, Providence, RI, USA

    Devasis Chatterjee & Todd M. Savarese

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  1. Devasis Chatterjee
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  2. Todd M. Savarese
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Additional information

This investigation was supported by PHS grants CA 38630 and CA 20892, by Research Career Development Award CA 01241 awarded by the National Cancer Institute, DHHS, and by grant BC-640 from the American Cancer Society (to T.M.S.). Support was also provided by an Advanced Predoctoral Fellowship Award from the Pharmaceutical Manufacturers Association (to D.C.)

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Chatterjee, D., Savarese, T.M. Posttranscriptional regulation of c-myc proto-oncogene expression and growth inhibition by recombinant human interferon-β ser17 in a human colon carcinoma cell line. Cancer Chemother. Pharmacol. 30, 12–20 (1992). https://doi.org/10.1007/BF00686479

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  • DOI: https://doi.org/10.1007/BF00686479

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