TY - JOUR
T1 - Modulation of growth gene expression by selective alteration of polyamines in human colon carcinoma cells
AU - Celano, Paul
AU - Berchtold, Craig M.
AU - Giardiello, Francis M.
AU - Casero, Robert A.
N1 - Funding Information:
ACKNOWLEDGMENTS: This research was supported by National Institutes of Health Grants CA 06973, CA 09071 and CA 43280 and the Clayton Fund. Dr. Celano is recipient of the Clinician-Scientist Award, The Johns Hopkins University School of Medicine. We thank Drs. S.B. Baylin, A. de Bustros, M. Mabry, and B. Nelkin for their helpful discussions and S. Ervin and J. Smith for their technical assistance and S. Lund and T. Hess for their administrative assistance and Dr. A.H. Owens, Jr. for his continuing support.
PY - 1989/11/30
Y1 - 1989/11/30
N2 - 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 diminshed. 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.
AB - 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 diminshed. 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.
UR - http://www.scopus.com/inward/record.url?scp=0024409042&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0024409042&partnerID=8YFLogxK
U2 - 10.1016/0006-291X(89)91082-6
DO - 10.1016/0006-291X(89)91082-6
M3 - Article
C2 - 2511847
AN - SCOPUS:0024409042
SN - 0006-291X
VL - 165
SP - 384
EP - 390
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 1
ER -