title: Chronic leptin treatment sensitizes MCF-7 breast cancer cells to estrogen.
abstract: OBJECTIVE
  Obesity is associated with an increased risk of estrogen-dependent breast cancer. The adipokine leptin, whose levels are chronically increased in obese people, has been shown to stimulate ER positive cancer cell growth. Considering previous evidence of a crosstalk between leptin and estrogen signaling, the objective of this study was to establish the influence of chronic leptin treatment on estrogen-dependent cell growth.
  
  
  METHODS
  To this aim, we use the estrogen receptor (ER) positive MCF-7 breast cancer cell line treated chronically with leptin and analyzed estrogen-dependent cell growth, ERs (ERα and ERβ) expression, ER-dependent transcriptional activity as well as cell survival to the antiestrogenic agents tamoxifen and ICI 182,780.
  
  
  RESULTS
  Leptin signaling pathway kept activated after chronic stimulation (7 days) with leptin showing significant phosphorylation of JAK2 and STAT3 and higher cell proliferation rate. Chronic leptin at 100 ng/mL dose increased ERα to ERβ ratio and consistently enhanced estrogen-dependent transcriptional activity, increasing E2-dependent cell growth and resistance to antiestrogen agents.
  
  
  CONCLUSIONS
  This study supports the existence of a crosstalk between leptin and estrogen, in which leptin might play an important role potentiating the mitogenic action of estrogen, probably by alteration of ERα to ERβ ratio.
authors.affiliation: Institut Universitari d'Investigació en Ciències de la Salut, Universitat de les Illes Balears, Ciber Fisiopatología Obesidad y Nutrición (CB06/03) Instituto Salud Carlos III, Palma de Mallorca, Spain. adamo.valle@uib.es
authors.forename: Adamo
authors.initials: A
authors.lastname: Valle
authors.forename: Jorge
authors.initials: J
authors.lastname: Sastre-Serra
authors.forename: Jordi
authors.initials: J
authors.lastname: Oliver
authors.forename: Pilar
authors.initials: P
authors.lastname: Roca
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D001943:Breast Neoplasms / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004958:Estradiol / Q000031:analogs & derivatives / Q000494:pharmacology; D047628:Estrogen Receptor alpha / Q000378:metabolism; D047629:Estrogen Receptor beta / Q000378:metabolism; D004967:Estrogens / Q000378:metabolism*; D005260:Female; D000077267:Fulvestrant; D006801:Humans; D053614:Janus Kinase 2 / Q000378:metabolism; D020738:Leptin / Q000494:pharmacology*; D010766:Phosphorylation; D050796:STAT3 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013629:Tamoxifen / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D004967:Estrogens; D020738:Leptin; D050796:STAT3 Transcription Factor; D013629:Tamoxifen; D000077267:Fulvestrant; D004958:Estradiol; D053614:Janus Kinase 2