Breast Cancer Research and Treatment

, Volume 35, Issue 2, pp 173–186 | Cite as

Effect of medroxyprogesterone acetate (MPA) and serum factors on cell proliferation in primary cultures of an MPA-induced mammary adenocarcinoma

  • Graciela Dran
  • Isabel A. Luthy
  • Alfredo A. Molinolo
  • Fernanda Montecchia
  • Eduardo H. Charreau
  • Christiane Dosne Pasqualini
  • Claudia Lanari


The effect of progesterone (Pg), medroxyprogesterone acetate (MPA), estradiol (E2), dihydrotestosterone (DHT) and dexamethasone (DEXA) was studied on thein vitro growth rate of a progestin-dependent (PD), estrogen-sensitive mammary tumor line originated in an MPA-treated BALB/c mouse (C4-HD), and on its estrogen-resistant variant (C4-HDR). The specificity of hormone action was further investigated using the anti-hormones RU-486 and hydroxyflutamide (FLU). Cell growth was evaluated in epithelial and fibroblastenriched cultures using3H-thymidine and/or autoradiography and immunocytochemistry. The results indicate that cell growth is directly stimulated by MPA and Pg at concentrations ranging from 10−11 to 10−7 M. RU486 prevented MPA-induced stimulation in concentrations 10 to 100 fold lower than those of MPA. When used alone, it inhibited cell proliferation only in concentrations higher than 10−11 M. At nM concentrations, neither DEXA nor DHT stimulated3H-thyrnidine uptake except DEXA at 100 nM. MPA-induced stimulation was not reverted by micromolar concentrations of FLU. As for E2 (10−7–10−9 M) it prevented MPA stimulation only in cultures of estrogen-sensitive tumors. Progesterone receptors (PR) (475 ± 115 fmoles/105 cells, n = 5) and estrogen receptors (ER) (ND-115 fmoles/105 cells, n = 5) were detected only in epithelial-enriched cultures. Serum from 7 day-MPA-treated mice induced a significant increase of3H-thymidine uptake; an increase was also obtained with serum from untreated ovariectomized animals to which 1 nM-100 nM concentrations of MPA had been added. The stimulatory effect of the exogenous MPA was much lower than that of the serum obtained from MPA-treated animals.

It is concluded that MPA stimulates cell growth of primary cultures of MPA-induced PD tumors via PR. The results provide support for a direct effect of MPA which may be mediated or potentiated by serum factors.

Key words

cell proliferation mammary tumors medroxyprogesterone acetate primary cultures progestins serum factors 


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Copyright information

© Kluwer Academic Publishers 1995

Authors and Affiliations

  • Graciela Dran
    • 1
  • Isabel A. Luthy
    • 1
  • Alfredo A. Molinolo
    • 1
  • Fernanda Montecchia
    • 1
  • Eduardo H. Charreau
    • 1
  • Christiane Dosne Pasqualini
    • 1
  • Claudia Lanari
    • 1
  1. 1.División Medicina Experimental, Instituto de Investigaciones HematológicasAcademia Nacional de Medicina & Instituto de Biología y Medicina ExperimentalBuenos AiresArgentina

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