Reversible suppression of c-myc expression in a human colon carcinoma line by the anticancer agent N-methylformamide.
The anticancer agent N-methylformamide (NMF), which at high concentrations (170 mM) induces cultured DLD-1 Clone A human colon carcinoma cells to increase their doubling times and lose their tumorigenicity in nude mice (Cordeiro, R.F., and Savarese, T.M. Cancer Res., 46: 1297-1305, 1986), suppresses the expression of the c-myc protooncogene in these cells in a dose- and time-dependent manner. This suppression involves an inhibition of c-myc transcription rather than an increased degradation of c-myc mRNA, and is reversed if NMF is removed from the culture medium. Expression of the glyceraldehyde 3-phosphate dehydrogenase gene, which is thought to be constitutive, is phosphate dehydrogenase gene, which is thought to be constitutive, is relatively unaffected by NMF treatment. The NMF-mediated decrease in c-myc expression may be associated with the ability of this agent to increase the doubling time of these cells, but there is no direct temporal link between the loss of c-myc expression and the NMF-induced loss of tumorigenicity.
Chatterjee
D
D
Division of Biology and Medicine, Brown University, Providence, Rhode Island 02912.
Mendelsohn
A
A
Shank
P R
PR
Savarese
T M
TM
D000970:Antineoplastic Agents / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D003110:Colonic Neoplasms / Q000235:genetics*; D005559:Formamides / Q000494:pharmacology*; D006801:Humans; D007700:Kinetics; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D016271:Proto-Oncogene Proteins c-myc; D011519:Proto-Oncogenes / Q000187:drug effects*; D012333:RNA, Messenger / Q000187:drug effects / Q000235:genetics; D013489:Suppression, Genetic / Q000187:drug effects*; D014158:Transcription, Genetic / Q000187:drug effects*
D000970:Antineoplastic Agents; D005559:Formamides; D011518:Proto-Oncogene Proteins; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger; C002950:methylformamide