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

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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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References

  1. Janne J, Poso H, Raina A: Polyamines in rapid growth and cancer. Biochem Biophys Acta 478: 241–293, 1978

    Google Scholar 

  2. Tabor CW, Tabor H: 1,4-Diaminobutane (putrescine), spermidine, and spermine. Annu Rev Biochem 45: 285–290, 1982

    Google Scholar 

  3. Chen KY, Presepe V, Parken N, Liu A: Changes of ornithine decarboxylase activity and polyamine content upon differentiation of mouse NB-15 neuroblastoma cells. J Cell Physiol 110: 285–290, 1982

    PubMed  Google Scholar 

  4. Schindler J, Kelly M, McCann P: Inhibition of ornithine decarboxylase induces embryonal carcinoma cell differentiation. Biochem Biophys Res Commun 114: 410–417, 1983

    PubMed  Google Scholar 

  5. Verma DS, Sunkara PS: An essential role for polyamine biosynthesis during human granulopoietic differentiation. Cancer Res 42: 3046–3049, 1982

    PubMed  Google Scholar 

  6. Kaye AM, Ickeson I, Linder HR: Stimulation by estrogens of ornithine and S-adenosylmethionine decarboxylases in the immature rat uterus. Biochem Biophys Acta 252: 150–159, 1973

    Google Scholar 

  7. Russell DH, Taylor RL: Polyamine synthesis and accumulation in the castrated rat uterus after estradiol 17β stimulation. Endocrinology 88: 1397–1403, 1971

    PubMed  Google Scholar 

  8. Lima G, Shiu RPC: Role of polyamines in estradiol-induced growth of human breast cancer cells. Cancer Res 45: 2466–2470, 1985

    PubMed  Google Scholar 

  9. Hoggard N, Green CD: Polyamines and growth regulation of cultured human breast cancer cells by 17β-oestradiol. Mol Cell Endocrinol 46: 71–78, 1986

    PubMed  Google Scholar 

  10. Kendra KL, Katzenellenbogen BS: An evaluation of the involvement of polyamines in modulating MCF-7 human breast cancer cell proliferation and progesterone receptor levels by estrogen and antiestrogen. J Steroid Biochem 28: 123–128, 1987

    PubMed  Google Scholar 

  11. Danzin C, Jung MJ, Claverie N, Grove J, Sjoerdsma A, Koch-Weser J: Effects of α-difluoromethylornithine, an enzyme-activated irreversible inhibitor of ornithine decarboxylase, on testosterone-induced regeneration of prostate and seminal vesicle in castrated rats. Biochem J 180: 507–513, 1979

    PubMed  Google Scholar 

  12. Rorke EA, Katzenellenbogen BS: Dissociated regulation of growth and ornithine decarboxylase activity by estrogen in the rat uterus. Biochem Res Commun 122: 1186–1193, 1984

    Google Scholar 

  13. Cheng SVY, Pollard JW: c-rasH and ornithine decarboxylase are induced by oestradiol-17β in the mouse uterine luminal epithelium independently of the proliferative status of the cell. FEBS Lett 196: 309–314, 1986

    PubMed  Google Scholar 

  14. Arafah BM, Finegan HM, Roe J, Manni A, Pearson OH: Hormone dependency in N-nitrosomethylurea-induced rat mammary tumors. Endocrinology 111: 584–588, 1982

    PubMed  Google Scholar 

  15. Manni A, Rainieri J, Arafah BM, Finegan HM, Pearson OH: Role of estrogen and prolactin in the growth and receptor levels of N-nitrosomethylurea-induced rat mammary tumors. Cancer Res 42: 3492–3495, 1982

    PubMed  Google Scholar 

  16. Manni A, Badger B, Glikman P, Bartholomew M, Santner S, Demers L: Individual and combined effects of α-difluoromethylornithine and ovariectomy on the growth and polyamine milieu of experimental breast cancer in rats. Cancer Res 49: 3529–3534, 1989

    PubMed  Google Scholar 

  17. Seiler N, Knodgen B: High performance liquid chromatographic procedure for the simultaneous determination of the natural polyamines and their monoacetyl derivatives. J Chromatogr 221: 227–235, 1980

    PubMed  Google Scholar 

  18. McGuire WC, De La Garza M, Chamness GC: Evaluation of estrogen receptor assays in human breast cancer tissue. Cancer Res 37: 637–639, 1977

    PubMed  Google Scholar 

  19. Feil PD, Klase JC, Margets MJ: Use of medroxyprogesterone acetate to measure cytosol progestin receptors in human breast cancer. Program of the 61st Annual Meeting of the Endocrine Society, Anaheim, CA. p. 150 1979

  20. Lancaster S, English HF, Demers LM, Manni A: Kinetic and morphometric responses of heterogeneous populations of experimental breast cancer cellsin vivo. Cancer Res 48: 3276–3281, 1988

    PubMed  Google Scholar 

  21. McGuire WL, Horwitz KB: A role for progesterone in breast cancer. Ann NY Acad Sci 286: 90–100, 1977

    PubMed  Google Scholar 

  22. Manni A, Wright C: Polyamines as mediators of estrogen action on the growth of experimental breast cancer in rats. J Natl Cancer Inst 73: 511–514, 1984

    PubMed  Google Scholar 

  23. Manni A, Wright C: Polyamines as mediators of the effect of prolactin and growth hormone on the growth of N-nitroso-N-methylurea-induced rat mammary tumor culturedin vitro in soft agar. J Natl Cancer Inst 74: 941–944, 1985

    PubMed  Google Scholar 

  24. Manni A, Badger G, Wright C, Ahmed SR, Demers LM: Effects of progestins on growth of experimental breast cancer in culture: Interaction with estradiol and prolactin and involvement of the polyamine pathway. Cancer Res 47: 3066–3071, 1987

    PubMed  Google Scholar 

  25. Cohen FJ, Manni A, Glikman P, Bartolomew M, Demers L: Involvement of the polyamine pathway in antistrogeninduced growth inhibition of human breast cancer. Cancer Res 48: 6819–6825, 1988

    PubMed  Google Scholar 

  26. Glikman P, Manni A, Demers L, Bartholomew M: Polyamine involvement in the growth of hormone-responsive and-resistant human breast cancer cells in culture. Cancer Res 49: 1371–1376, 1989

    PubMed  Google Scholar 

  27. Manni A, Badger B, Luk G,et al: role of polymanies in the growth of hormone-responsive experimental breast cancerin vivo. Breast Cancer Res Treat 11: 231–240, 1988

    PubMed  Google Scholar 

  28. Viladiu P, Delgado C, Pensky J, Pearson OH: Estrogen binding protein of rat liver. Endocrine Res Commun 2: 273–280, 1975

    Google Scholar 

  29. Manni A, Chambers MJ, Pearson OH: Prolactin induces its own receptors in rat liver. Endocrinology 103: 2168–2171, 1978

    PubMed  Google Scholar 

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Manni, A., Badger, B., Lynch, J. et al. Selectivity of polyamine involvement in hormone action on normal and neoplastic target tissues of the rat. Breast Cancer Res Tr 17, 187–196 (1991). https://doi.org/10.1007/BF01806368

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