Skip to main content
SpringerLink
Log in

Polyamines and the synthesis of estradiol-regulated growth factors in rat mammary cancer in culture

  • Report
  • Published:
Breast Cancer Research and Treatment Aims and scope Submit manuscript

Abstract

We have recently provided evidence to suggest that the polyamine pathway plays an essential role in the expression of the growth-promoting effect of estradiol (E2) regulated growth factors in the N-nitrosomethylurea (NMU) induced rat mammary tumor culturedin vitro in the soft agar clonogenic assay. To further explore the interaction between the polyamine pathway and autocrine control of tumor growth by E2, we tested whether, in our system, polyamines play a role in the synthesis of E2-regulated growth factors. Conditioned medium (CM) obtained from tumors treated with E2 and the polyamine biosynthesis inhibitor α-difluoromethyl-ornithine (DFMO) (1 mM) no longer exhibited the colony-stimulating effect which was consistently observed with E2-CM. Such growth promoting activity was restored in a dose-dependent fashion with CM obtained from tumors treated with E2, DFMO, and increasing concentrations of spermidine (from 1 to 100µM). Conditioned medium obtained from tumors treated with DFMO with and without spermidine in the absence of E2 had no discernible effects on colony formation. The colony stimulating effect of the CM employed could not be accounted for by the contaminating presence in the media of E2, DFMO, or polyamines. These results indicate that, in our system, the polyamine pathway plays an important role in the synthesis of E2-regulated growth factors.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

References

  1. Chalbos DF, Vignon F, Keydar I, Rochefort H: Estrogens stimulate cell proliferation and induce secretory proteins in a human breast cancer cell line (T47D). J Clin Endocrinol Metab 55: 276–283, 1982

    PubMed  Google Scholar 

  2. Vignon F, Lippman ME, Nawata H, Derocq D, Rochefort H: Induction of two estrogen-responsive proteins by antiestrogens in R27, a tamoxifen-resistant clone of MCF-7 cells. Cancer Res 44: 2084–2088, 1984

    PubMed  Google Scholar 

  3. Vignon F, Derocq D, Chambon M, Rochefort H: Les proteins 4: oestrogeno-induites secretees par les cellules mammaires cancereures humaines MCF7 stimulent leur proliferation. CR Acad Sci Paris 296: 151–156, 1983

    Google Scholar 

  4. Ikeda T, Danielpour D, Sirbasku DA: Isolation and properties of endocrine and autocrine type mammary tumor cell growth factors (estromedins). Bresciani F, King RJB, Lippman ME, Namer M, Raynaud JP (eds): Progress in Cancer Research and Therapy. Raven Press, New York, 1984, vol. 31: 171–186

    Google Scholar 

  5. Zwiebel JA, Davis MR, Kohn E, Solomon DS, Kidwell WR: Anchorage-independent growth-conferring factor production by rat mammary tumor cells. Cancer Res 42: 5117–5125, 1982

    PubMed  Google Scholar 

  6. Hiragun A, Yoshida Y, Sato M, Tominaga T, Mitsui H: Isolation of two syngeneic cell lines from a rat mammary carcinoma: Growth factor production by neoplastic epithelial cells. J Nat Cancer Inst 75: 471–482, 1985

    PubMed  Google Scholar 

  7. Manni A, Wright C, Feil P, Baranao L, Demers L, Garcia M, Rochefort H: Autocrine stimulation by estradiol-regulated growth factors of rat hormone-responsive mammary cancer: Interaction with the polyamine pathway. Cancer Res 46: 1594–1598, 1986

    PubMed  Google Scholar 

  8. 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 

  9. Manni A, Wright C: Effect of tamoxifen and α-difluoromethyl-ornithine on clones of nitrosomethylurea-induced rat mammary tumor cells grown in soft agar. Cancer Res 43: 1084–1088, 1983

    PubMed  Google Scholar 

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

    PubMed  Google Scholar 

  11. Berthois Y, Katzenellenbogen JA, Katzenellenbogen BS: Phenol red in tissue culture media is a weak estrogen: Implications concerning the study of estrogen-responsive cells in culture. Proc Natl Acad Sci USA 83: 2496–2500, 1986

    PubMed  Google Scholar 

  12. Manni A, Wright C: Assessment of mitogenesis of the hormone-responsive N-nitrosomethylurea-induced rat mammary tumor grown in culture in soft agar using3H-thymidine incorporation into DNA. Breast Cancer Res Treat 3: 287–292, 1983

    PubMed  Google Scholar 

  13. Von Hoff DD, Casper J, Bradley E, Trent JM, Hodach A, Reichert C, Makuch R, Altman A: Direct cloning of human neuroblastoma cells in soft agar culture. Cancer Res 40: 3591–3597, 1980

    PubMed  Google Scholar 

  14. Arafah BM, Wilhite BL, Rainieri J, Brodkey JS, Pearson OH: Inhibitory action of bromocriptine and tamoxifen on the growth of human pituitary tumors in soft agar. J Clin Endocrinol Metab 57: 986–992, 1983

    PubMed  Google Scholar 

  15. Bradley EC, Reichert CM, Brennan MF, Von Hoff DD: Direct cloning of human parathyroid hyperplasia cells in soft agar culture. Cancer Res 40: 3694–3696, 1980

    PubMed  Google Scholar 

  16. Bradford MM: A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 72: 248–254, 1976

    PubMed  Google Scholar 

  17. Haning RV, Meier SM, Boehnlein LM, Garrity M, Shapiro SS: Two direct radioimmunoassays for 17β-estradiol evaluation for use in monitoringin vitro fertilization. Clin Chem 30: 787–790, 1984

    PubMed  Google Scholar 

  18. Luk GD, Baylin SB: Inhibition of intestinal epithelial DNA synthesis and adaptive hyperplasia after jejunectomy in the rat by suppression of polyamine biosynthesis. J Clin Invest 74: 698–704, 1984

    PubMed  Google Scholar 

  19. Grove J, Fozard JR, Mammont PS: Assay of α-difluoromethyl-ornithine in body fluids and tissues by automatic amino-acid analysis. J Chromatogr 223: 409–416, 1981

    PubMed  Google Scholar 

  20. Winer BJ: Statistical Principles in Experimental Design (2nd Ed). McGraw-Hill, New York, 1971, pp. 185–196

    Google Scholar 

  21. 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 

  22. Manni A, Wright C: Reversal of the antiproliferative effect of the antiestrogen tamoxifen by polyamines in breast cancer cells. Endocrinology 114: 836–839, 1984

    PubMed  Google Scholar 

  23. 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 

  24. Manni A, Pontari M, Wright C: Autocrine stimulation by prolactin of hormone-responsive breast cancer growth in culture. Endocrinology 117: 2040–2043, 1985

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Departments of Medicine and Pathology, Division of Endocrinology, The Milton S. Hershey Medical Center, P.O. Box 850, 17033, Hershey, PA, USA

    Andrea Manni, Carol Wright, Gordon D. Luk, Glenn Davis & Lawrence M. Demers

  2. Department of Medicine and the Oncology Center, The Johns Hopkins University School of Medicine, 21205, Baltimore, MD, USA

    Andrea Manni, Carol Wright, Gordon D. Luk, Glenn Davis & Lawrence M. Demers

Authors
  1. Andrea Manni
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Carol Wright
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Gordon D. Luk
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Glenn Davis
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Lawrence M. Demers
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Manni, A., Wright, C., Luk, G.D. et al. Polyamines and the synthesis of estradiol-regulated growth factors in rat mammary cancer in culture. Breast Cancer Res Tr 9, 45–51 (1987). https://doi.org/10.1007/BF01806693

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01806693

Keywords

Search

Navigation