title: Aromatase expression in leptin-pretreated human breast pre-adipocytes is enhanced by zeranol and suppressed by (-)-gossypol.
abstract: BACKGROUND
  Obesity is associated with an increased risk of estrogen-dependent breast cancer. Recently, concerns have been raised regarding the role of zeranol (Z), a non-steroidal anabolic growth promoter with potent estrogenic activity widely used in the U.S.A. beef industry, as a possible contributor to an increased incidence of human breast cancer. This study hypothesized that obese individuals may be at greater risk of developing zeranol-induced breast cancer.
  
  
  METHODS
  The aromatase mRNA expression level of three cell types isolated from adipose tissues were assayed by RT-PCR, and the cell proliferation of primary cultured human normal breast pre-adipocytes (HNBPADs) was investigated using the CellTiter96® non-radioactive method. The effects of Z and gossypol on aromatase expression of leptin-pretreated HNBPADs were evaluated by RT-PCR.
  
  
  RESULTS
  HNBPADs expressed higher aromatase than primary cultured human breast epithelial cells and stromal cells. Z enhanced the mitogenic activity of leptin and increased aromatase expression in HNBPADs. Moreover, (-)-gossypol counteracted Z- and leptin-induced cell proliferation and aromatase expression.
  
  
  CONCLUSIONS
  These results suggested that bioactive Z metabolites contained in meat produced from Z-implanted beef cattle may increase estrogen biosynthesis in obese individuals by increasing aromatase expression and estrogen production, which will promote cell sensitivity and increase breast cancer cell growth.
authors.affiliation: College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, PR China.
authors.forename: Saiyi
authors.initials: S
authors.lastname: Zhong
authors.forename: Wei-Ping
authors.initials: WP
authors.lastname: Ye
authors.forename: Ping-Ping
authors.initials: PP
authors.lastname: Xu
authors.forename: Eric
authors.initials: E
authors.lastname: Feng
authors.forename: Hong
authors.initials: H
authors.lastname: Li
authors.forename: Shu-Hong
authors.initials: SH
authors.lastname: Lin
authors.forename: Jie-Yu
authors.initials: JY
authors.lastname: Liu
authors.forename: Changwei
authors.initials: C
authors.lastname: Ma
authors.forename: Young C
authors.initials: YC
authors.lastname: Lin
mesh_terms: D017667:Adipocytes / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D001141:Aromatase / Q000096:biosynthesis* / Q000235:genetics; D001940:Breast / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D001943:Breast Neoplasms / Q000139:chemically induced / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D048708:Cell Growth Processes / Q000187:drug effects; D004968:Estrogens, Non-Steroidal / Q000494:pharmacology / Q000506:poisoning; D006072:Gossypol / Q000494:pharmacology*; D006801:Humans; D020738:Leptin / Q000494:pharmacology*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D011994:Recombinant Proteins / Q000494:pharmacology; D017154:Stromal Cells / Q000166:cytology / Q000187:drug effects / Q000201:enzymology; D015029:Zeranol / Q000494:pharmacology* / Q000506:poisoning
chemical_list: D004968:Estrogens, Non-Steroidal; D020738:Leptin; D012333:RNA, Messenger; D011994:Recombinant Proteins; D015029:Zeranol; D001141:Aromatase; D006072:Gossypol