title: Breast cyst fluids increase the proliferation of breast cell lines in correlation with their hormone and growth factor concentration.
abstract: OBJECTIVE
  Gross cystic disease (GCD) of the breast is reported to occur in 7% of women in the developed world and, although not premalignant, is thought to be associated with an increased risk of breast cancer. Hormone and growth factor concentration levels were measured in breast cyst fluid (BCF) to correlate them with their mitogenic activity in tumour (MCF-7) or nontransformed (MCF-10A) cells.
  
  
  RESULTS
  Oestradiol (E2), oestrone (E1), E2-sulfate (E2-S), E1-sulfate (E1-S) and epidermal growth factor (EGF) concentrations were, as expected, significantly higher in type I than in type II cysts, while transforming growth factor-beta 2 (TGF-beta2) showed higher levels in type II cysts. Fifty per cent of the BCF samples stimulated [3H]-thymidine incorporation into MCF-7 cells while 34.5% inhibited this parameter. In MCF-10A cells, most BCF samples were stimulatory (85%). E2, E1 and EGF concentrations in BCF samples correlated significantly and positively with cell proliferation in MCF-7 cells, whereas a significant negative correlation was found for TGF-beta2. In MCF-10A cells, only E2-S and E1-S exhibited significant positive correlation, whereas a significant negative correlation was found for TGF-beta2. Progesterone (Pg), E2 and EGF incubated under the same conditions had a stimulatory effect on [3H]-thymidine incorporation into MCF-7 cells, whereas TGF-beta2 inhibited this parameter. Pg, E2, E1 and EGF significantly stimulated this parameter in MCF-10A cells.
  
  
  CONCLUSIONS
  The stimulatory action of BCF on cell proliferation in a model of human breast epithelial cells could partly explain the increased incidence of breast cancer in cyst-bearing women.
authors.affiliation: Instituto de Biología y Medicina Experimental, Buenos Aires, Argentina.
authors.forename: Pablo J
authors.initials: PJ
authors.lastname: Enriori
authors.forename: Stella Maris
authors.initials: SM
authors.lastname: Vázquez
authors.forename: Violeta
authors.initials: V
authors.lastname: Chiauzzi
authors.forename: Cecilia
authors.initials: C
authors.lastname: Pérez
authors.forename: Carlos R
authors.initials: CR
authors.lastname: Fischer
authors.forename: Jorge R
authors.initials: JR
authors.lastname: Gori
authors.forename: Alberto E
authors.initials: AE
authors.lastname: Etkin
authors.forename: Eduardo
authors.initials: E
authors.lastname: Charreau
authors.forename: Ricardo S
authors.initials: RS
authors.lastname: Calandra
authors.forename: Isabel A
authors.initials: IA
authors.lastname: Lüthy
mesh_terms: D000328:Adult; D001826:Body Fluids / Q000737:chemistry / Q000378:metabolism; D047688:Breast Cyst / Q000378:metabolism*; D045744:Cell Line, Tumor / Q000378:metabolism / Q000473:pathology*; D049109:Cell Proliferation; D004815:Epidermal Growth Factor / Q000032:analysis; D004847:Epithelial Cells / Q000473:pathology; D005260:Female; D013006:Growth Hormone / Q000378:metabolism*; D006728:Hormones / Q000378:metabolism*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000032:analysis; D007334:Insulin-Like Growth Factor I / Q000032:analysis; D011188:Potassium / Q000032:analysis; D012964:Sodium / Q000032:analysis; D016212:Transforming Growth Factor beta / Q000032:analysis
chemical_list: D006728:Hormones; D018972:Insulin-Like Growth Factor Binding Protein 3; D016212:Transforming Growth Factor beta; D004815:Epidermal Growth Factor; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone; D012964:Sodium; D011188:Potassium