Alteration of cellular oncogene expression in L1210 cells by a nitrosourea analog of thymidine.
3'[3-(2-Chloroethyl)-3'nitrosoureido]-3'-deoxythymidine (3'-CTNU), a chloroethylnitrosourea analog of thymidine, is a potent antineoplastic agent against murine leukemia L1210. In this study, we have examined the effects of 3'-CTNU on cellular oncogene (proto-oncogene) expression. We found that the expression of the c-myb proto-oncogene was dramatically enhanced in a concentration- and time-dependent manner by 3'-CTNU in murine leukemia L1210 cells, whereas the expression of the c-myc proto-oncogene was suppressed. The enhancement of c-myb gene expression was found to be cell type-specific and to involve an increase of the c-myb transcription rate rather than an alteration of c-myb gene structure or increased stability of c-myb mRNA. Further analysis demonstrated that the altered c-myb gene expression was largely due to the presence of 3'-amino-3'-deoxythymidine, a decomposition product of 3'-CNTU. The expression of five other proto-oncogenes was unaffected by 3'-CTNU treatment. Our study showed that an antineoplastic agent can increase or decrease the expression of proto-oncogenes.
Zhang
X K
XK
Department of Biochemistry, University of Vermont College of Medicine, Burlington 05405.
Zucker
M L
ML
Huang
D P
DP
Lin
T S
TS
Prusoff
W H
WH
Chiu
J F
JF
D000199:Actins / Q000096:biosynthesis; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D015152:Blotting, Northern; D015139:Blotting, Southern; D004247:DNA / Q000032:analysis; D015224:Dideoxynucleosides / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D016259:Genes, myc / Q000187:drug effects; D007939:Leukemia L1210 / Q000188:drug therapy* / Q000378:metabolism; D051379:Mice; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis; D020598:Proto-Oncogene Proteins c-myb; D011519:Proto-Oncogenes / Q000187:drug effects*; D012313:RNA / Q000032:analysis; D013997:Time Factors; D014158:Transcription, Genetic / Q000187:drug effects; D014407:Tumor Cells, Cultured
D000199:Actins; D000970:Antineoplastic Agents; D015224:Dideoxynucleosides; D011518:Proto-Oncogene Proteins; D020598:Proto-Oncogene Proteins c-myb; D012313:RNA; C027799:3'-(3-(2-chloroethyl)-3-nitrosourea)-3'-deoxythymidine; D004247:DNA