Selectivity of polyamine involvement in hormone action on normal and neoplastic target tissues of the rat

Andrea Manni, Betty Badger, James Lynch, Laurence Demers

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

The present experiments were designed to evaluate the polyamine involvement in hormonal actions on proliferation and receptor content of neoplastic tissue (hormone-responsive breast cancer) as well as on growth of normal endocrine target tissue (uterus) in the same animals. Administration of estradiol and perphenazine (to stimulate endogenous prolactin release) stimulated N-nitrosomethyl-urea (NMU)-induced rat mammary tumor growth following ovariectomy-induced tumor regression. Such hormonal activation of breast cancer growth was completely abolished by treatment with α-difluoromethyl-ornithine (DFMO), a specific irreversible inhibitor of ornithine decarboxylase, which lowered tumor content of polyamines. The growth inhibitory effect of DFMO was partially reversible by exogenous putrescine administration. In contrast, the rise in cytosolic content of progesterone receptors induced by hormonal treatment was not affected by suppression of tumor polyamine levels by DFMO. Similarly, DFMO administration failed to influence the hormone-induced increase in uterine weight in the same animals. Thus, our data suggest selectivity of polyamine involvement in hormone actions, which, in our experimental system, seems to be restricted to the endocrine control of neoplastic cell proliferation.

Original languageEnglish (US)
Pages (from-to)187-196
Number of pages10
JournalBreast Cancer Research and Treatment
Volume17
Issue number3
DOIs
StatePublished - Jan 1 1991

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Ornithine
Polyamines
Hormones
Breast Neoplasms
Growth
Perphenazine
Neoplasms
Putrescine
Ovariectomy
Progesterone Receptors
Prolactin
Uterus
Urea
Estradiol
Cell Proliferation
Weights and Measures

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

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abstract = "The present experiments were designed to evaluate the polyamine involvement in hormonal actions on proliferation and receptor content of neoplastic tissue (hormone-responsive breast cancer) as well as on growth of normal endocrine target tissue (uterus) in the same animals. Administration of estradiol and perphenazine (to stimulate endogenous prolactin release) stimulated N-nitrosomethyl-urea (NMU)-induced rat mammary tumor growth following ovariectomy-induced tumor regression. Such hormonal activation of breast cancer growth was completely abolished by treatment with α-difluoromethyl-ornithine (DFMO), a specific irreversible inhibitor of ornithine decarboxylase, which lowered tumor content of polyamines. The growth inhibitory effect of DFMO was partially reversible by exogenous putrescine administration. In contrast, the rise in cytosolic content of progesterone receptors induced by hormonal treatment was not affected by suppression of tumor polyamine levels by DFMO. Similarly, DFMO administration failed to influence the hormone-induced increase in uterine weight in the same animals. Thus, our data suggest selectivity of polyamine involvement in hormone actions, which, in our experimental system, seems to be restricted to the endocrine control of neoplastic cell proliferation.",
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Selectivity of polyamine involvement in hormone action on normal and neoplastic target tissues of the rat. / Manni, Andrea; Badger, Betty; Lynch, James; Demers, Laurence.

In: Breast Cancer Research and Treatment, Vol. 17, No. 3, 01.01.1991, p. 187-196.

Research output: Contribution to journalArticle

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