title: Synthetic progestins induce growth and metastasis of BT-474 human breast cancer xenografts in nude mice.
abstract: OBJECTIVE
  Previous studies have shown that sequential exposure to estrogen and progesterone or medroxyprogesterone acetate (MPA) stimulates vascularization and promotes the progression of BT-474 and T47-D human breast cancer cell xenografts in nude mice (Liang et al, Cancer Res 2007, 67:9929). In this follow-up study, the effects of progesterone, MPA, norgestrel (N-EL), and norethindrone (N-ONE) on BT-474 xenograft tumors were compared in the context of several different hormonal environments. N-EL and N-ONE were included in the study because synthetic progestins vary considerably in their biological effects and the effects of these two progestins on the growth of human tumor xenografts are not known.
  
  
  METHODS
  Estradiol-supplemented intact and ovariectomized immunodeficient mice were implanted with BT-474 cells. Progestin pellets were implanted simultaneously with estradiol pellets either 2 days before tumor cell injection (ie, combined) or 5 days after tumor cell injections (ie, sequentially).
  
  
  RESULTS
  Progestins stimulated the growth of BT-474 xenograft tumors independent of exposure timing and protocol, MPA stimulated the growth of BT-474 xenograft tumors in ovariectomized mice, and progestins stimulated vascular endothelial growth factor elaboration and increased tumor vascularity. Progestins also increased lymph node metastasis of BT-474 cells. Therefore, progestins, including N-EL and N-ONE, induce the progression of breast cancer xenografts in nude mice and promote tumor metastasis.
  
  
  CONCLUSIONS
  These observations suggest that women who ingest progestins for hormone therapy or oral contraception could be more at risk for developing breast cancer because of proliferation of existing latent tumor cells. Such risks should be considered in the clinical setting.
authors.affiliation: Department of Biomedical Sciences, University of Missouri, Columbia, MO 65211, USA.
authors.forename: Yayun
authors.initials: Y
authors.lastname: Liang
authors.forename: Indira
authors.initials: I
authors.lastname: Benakanakere
authors.forename: Cynthia
authors.initials: C
authors.lastname: Besch-Williford
authors.forename: Ryyan S
authors.initials: RS
authors.lastname: Hyder
authors.forename: Mark R
authors.initials: MR
authors.lastname: Ellersieck
authors.forename: Salman M
authors.initials: SM
authors.lastname: Hyder
mesh_terms: D000818:Animals; D001943:Breast Neoplasms; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D005260:Female; D020249:Hormone Replacement Therapy / Q000009:adverse effects*; D008207:Lymphatic Metastasis; D051379:Mice; D008819:Mice, Nude; D009640:Norethindrone / Q000494:pharmacology*; D009644:Norgestrel / Q000494:pharmacology*; D045167:Progesterone Congeners / Q000494:pharmacology*; D014183:Transplantation, Heterologous
chemical_list: D045167:Progesterone Congeners; D009644:Norgestrel; D009640:Norethindrone
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