title: Growth hormone excess promotes breast cancer chemoresistance.
abstract: BACKGROUND
  GH and IGF-I are known to promote breast carcinogenesis. Even if breast cancer (BC) incidence is not increased in female acromegalic patients, mortality is greater as compared with general population.
  
  
  OBJECTIVE
  The objective of the study was to evaluate whether GH/IGF-I excess might influence BC response to chemotherapy.
  
  
  METHODS
  We evaluated GH and IGF-I effects on cell proliferation of a BC cell line, MCF7 cells, in the presence of doxorubicin (Doxo), frequently used in BC chemotherapy, and the possible mechanisms involved.
  
  
  RESULTS
  GH and IGF-I induce MCF7 cell growth in serum-free conditions and protect the cells from the cytotoxic effects of Doxo. GH effects are direct and not mediated by IGF-I because they are apparent also in the presence of an IGF-I receptor blocking antibody and disappear in the presence of the GH antagonist pegvisomant. The expression of the MDR1 gene, involved in resistance to chemotherapeutic drugs, was not induced by GH. In addition, c-fos transduction was reduced by Doxo, which prevented GH stimulatory effects. Pegvisomant inhibited basal and GH-induced c-fos promoter transcriptional activity. Autocrine GH action is ruled out by the lack of endogenous GH expression in this MCF7 cell strain.
  
  
  CONCLUSIONS
  These data indicate that GH can directly induce resistance to chemotherapeutic drugs with a mechanism that might involve GH-induced early gene transcription and support the hypothesis that GH excess can hamper BC treatment, possibly resulting in an increased mortality.
authors.affiliation: Section of Endocrinology, Department of Biomedical Sciences and Advanced Therapies, University of Ferrara, 44100 Ferrara, Italy.
authors.forename: Maria Chiara
authors.initials: MC
authors.lastname: Zatelli
authors.forename: Mariella
authors.initials: M
authors.lastname: Minoia
authors.forename: Daniela
authors.initials: D
authors.lastname: Molè
authors.forename: Valentina
authors.initials: V
authors.lastname: Cason
authors.forename: Federico
authors.initials: F
authors.lastname: Tagliati
authors.forename: Angelo
authors.initials: A
authors.lastname: Margutti
authors.forename: Marta
authors.initials: M
authors.lastname: Bondanelli
authors.forename: Maria Rosaria
authors.initials: MR
authors.lastname: Ambrosio
authors.forename: Ettore
authors.initials: E
authors.lastname: degli Uberti
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics*; D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism* / Q000401:mortality; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D005260:Female; D005455:Fluorescent Antibody Technique; D015972:Gene Expression Regulation, Neoplastic; D019382:Human Growth Hormone / Q000378:metabolism*; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D008156:Luciferases; D008875:Middle Aged; D017526:Receptor, IGF Type 1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I; D008156:Luciferases; D017526:Receptor, IGF Type 1