title: Mifepristone inhibits MPA-and FGF2-induced mammary tumor growth but not FGF2-induced mammary hyperplasia.
abstract: We have previously demonstrated a crosstalk between fibroblast growth factor 2 (FGF2) and progestins inducing experimental breast cancer growth. The aim of the present study was to compare the effects of FGF2 and of medroxyprogesterone acetate (MPA) on the mouse mammary glands and to investigate whether the antiprogestin RU486 was able to reverse the MPA- or FGF2-induced effects on both, mammary gland and tumor growth. We demonstrate that FGF2 administered locally induced an intraductal hyperplasia that was not reverted by RU486, suggesting that FGF2-induced effects are progesterone receptor (PR)-independent. However, MPA-induced paraductal hyperplasia was reverted by RU486 and a partial agonistic effect was observed in RU486-treated glands. Using C4-HD tumors which only grow in the presence of MPA, we showed that FGF2 administered intratumorally was able to stimulate tumor growth as MPA. The histology of FGF2-treated tumors showed different degrees of gland differentiation. RU486 inhibited both, MPA or FGF2 induced tumor growth. However, only complete regression was observed in MPA-treated tumors. Our results support the hypothesis that stromal FGF2 activates PR inducing hormone independent tumor growth.
authors.affiliation: Laboratorio de Carcinogénesis Hormonal, Instituto de Biología y Medicina Experimental (IBYME)- Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Buenos Aires, Argentina.
authors.forename: Juan P
authors.initials: JP
authors.lastname: Cerliani
authors.forename: Sebastián
authors.initials: S
authors.lastname: Giulianelli
authors.forename: Ana
authors.initials: A
authors.lastname: Sahores
authors.forename: Victoria
authors.initials: V
authors.lastname: Wargon
authors.forename: Adrian
authors.initials: A
authors.lastname: Gongora
authors.forename: Alberto
authors.initials: A
authors.lastname: Baldi
authors.forename: Alfredo
authors.initials: A
authors.lastname: Molinolo
authors.forename: Caroline E
authors.initials: CE
authors.lastname: Lamb
authors.forename: Claudia
authors.initials: C
authors.lastname: Lanari
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000037:antagonists & inhibitors*; D006727:Hormone Antagonists / Q000494:pharmacology*; D006965:Hyperplasia / Q000139:chemically induced; D008321:Mammary Glands, Animal / Q000187:drug effects* / Q000473:pathology; D015674:Mammary Neoplasms, Animal / Q000139:chemically induced / Q000188:drug therapy*; D017258:Medroxyprogesterone Acetate / Q000037:antagonists & inhibitors*; D051379:Mice; D015735:Mifepristone / Q000494:pharmacology*
chemical_list: D006727:Hormone Antagonists; D016222:Fibroblast Growth Factor 2; D015735:Mifepristone; D017258:Medroxyprogesterone Acetate