Modulation of growth gene expression by selective alteration of polyamines in human colon carcinoma cells.
The biosynthesis of the polyamines, putrescine, spermidine and spermine, is temporally linked with expression of many growth related genes. Our previous studies have shown that generalized polyamine depletion of the human colon cancer cell line COLO 320 by 2-difluoromethylornithine is associated with decreased transcription of the c-myc, c-fos, and ornithine decarboxylase (ODC) genes. In the current study, the role of individual polyamines was further defined by the use of a specific inhibitor of spermidine synthase, S-adenosyl-1,8, diamino-3-thio-octane (AdoDATO), and a spermine analogue, N1,N12 bis(ethyl)spermine. Our data demonstrate that depletion of spermidine results in a 60-90% decrease in c-myc mRNA steady state levels. In contrast, c-fos mRNA levels are decreased only when both spermidine and spermine are diminished. Furthermore, ODC mRNA levels are increased when all polyamines are decreased by DFMO, but are unaffected by a selective reduction in intracellular spermidine levels by AdoDATO. These studies suggest that individual polyamines may have a selective role in the expression of specific growth related genes.
Celano
P
P
Johns Hopkins Oncology Center, Baltimore, Maryland.
Berchtold
C M
CM
Giardiello
F M
FM
Casero
R A
RA
D000241:Adenosine / Q000494:pharmacology / Q000031:analogs & derivatives; D015152:Blotting, Northern; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D003110:Colonic Neoplasms; D000518:Eflornithine / Q000494:pharmacology*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D011073:Polyamines / Q000378:metabolism*; D011519:Proto-Oncogenes / Q000187:drug effects*; D011700:Putrescine / Q000378:metabolism; D012333:RNA, Messenger / Q000187:drug effects / Q000235:genetics; D013095:Spermidine / Q000378:metabolism; D013096:Spermine / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects; D014407:Tumor Cells, Cultured / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism
D011073:Polyamines; D012333:RNA, Messenger; D013096:Spermine; C027548:S-adenosyl-3-thio-1,8-diaminooctane; D000241:Adenosine; D013095:Spermidine; D011700:Putrescine; D000518:Eflornithine