TY - JOUR
T1 - Polyamines as mediators of estrogen action on the growth of experimental breast cancer in rats
AU - Manni, Andrea
AU - Wright, Carol
N1 - Funding Information:
1 Received December 23, 1983; accepted March 28, 1984. 2 Supported in part by Public Health Service contract NOICB-53851 from the Division of Cancer Biology and Diagnosis, National Cancer Institute; and by an institutional research grant from the American Cancer Society. 'Endocrinology Division. Department of Medicine, The Milton S. Hershey Medical Center. The Pennsylvania State University. P.O. Box 850. Hershey. Pa. 17033. 4 We thank Dr. Richard J. Santen and Dr. james M. Hammond for their helpful suggestions and Mrs. Marlene Thompson for her secretarial assistance.
PY - 1984/8
Y1 - 1984/8
N2 - The role of polyamines as mediators of the mitogenic effect of 17β-estradiol (E2) was investigated in the N-nitrosomethylurea [(NMU) CAS: 684-93-5; N-methyl-N-nitroso-urea]-induced Sprague-Dawley rat mammary tumor grown in the soft agar clonogenic assay under serum-free medium conditions. Inhibition of polyamine biosynthesis with α-difluoromethylomithine (DFMO) (1 mM), an irreversible inhibitor of ornithine decarboxylase, completely blocked the growth-promoting effect of E2 (10−8 M) in this system. Exogenous administration of putrescine (2.5 mM), spermidine (0.1 mM), and spermine (0.1 mM) reversed the inhibitory effect of DFMO and completely restored the action of E2. These polyamines, however, had no effect on tumor growth when they were added alone in identical concentrations. The results indicate that polyamines are essential but probably not sufficient in mediating the E2 effect on the growth of the NMU-induced mammary tumor under these experimental conditions.
AB - The role of polyamines as mediators of the mitogenic effect of 17β-estradiol (E2) was investigated in the N-nitrosomethylurea [(NMU) CAS: 684-93-5; N-methyl-N-nitroso-urea]-induced Sprague-Dawley rat mammary tumor grown in the soft agar clonogenic assay under serum-free medium conditions. Inhibition of polyamine biosynthesis with α-difluoromethylomithine (DFMO) (1 mM), an irreversible inhibitor of ornithine decarboxylase, completely blocked the growth-promoting effect of E2 (10−8 M) in this system. Exogenous administration of putrescine (2.5 mM), spermidine (0.1 mM), and spermine (0.1 mM) reversed the inhibitory effect of DFMO and completely restored the action of E2. These polyamines, however, had no effect on tumor growth when they were added alone in identical concentrations. The results indicate that polyamines are essential but probably not sufficient in mediating the E2 effect on the growth of the NMU-induced mammary tumor under these experimental conditions.
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U2 - 10.1093/jnci/73.2.511
DO - 10.1093/jnci/73.2.511
M3 - Article
C2 - 6431170
AN - SCOPUS:0021179294
SN - 0027-8874
VL - 73
SP - 511
EP - 514
JO - Journal of the National Cancer Institute
JF - Journal of the National Cancer Institute
IS - 2
ER -
