Posttranscriptional regulation of c-myc proto-oncogene expression and growth inhibition by recombinant human interferon-beta ser17 in a human colon carcinoma cell line.
Recombinant human interferon-beta ser17 (IFN-beta 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-1 Clone A human colon-carcinoma cells. The suppression of c-myc expression mediated by IFN-beta 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-beta 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-beta ser17 and the anticancer agent N-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-beta ser17-mediated suppression of c-myc expression and the induction of 2',5'-oligo (A) synthetase activity in DLD-1 clone A cells.
Chatterjee
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Division of Biology and Medicine, Brown University, Providence, RI 02912.
Savarese
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TM
D015088:2',5'-Oligoadenylate Synthetase / Q000187:drug effects / Q000378:metabolism; D000970:Antineoplastic Agents / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism; D005559:Formamides / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D016259:Genes, myc / Q000187:drug effects / Q000235:genetics*; D006801:Humans; D000068556:Interferon beta-1a; D000068576:Interferon beta-1b; D016899:Interferon-beta / Q000494:pharmacology*; D000090063:Proto-Oncogene Mas; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D012260:Ribonucleases / Q000378:metabolism; D014158:Transcription, Genetic / Q000235:genetics*; D014407:Tumor Cells, Cultured / Q000187:drug effects
D000970:Antineoplastic Agents; D005559:Formamides; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D012333:RNA, Messenger; D011994:Recombinant Proteins; D000068576:Interferon beta-1b; D016899:Interferon-beta; D015088:2',5'-Oligoadenylate Synthetase; D012260:Ribonucleases; C002950:methylformamide; D000068556:Interferon beta-1a