title: Testosterone regulates cell proliferation in aggressive fibromatosis (desmoid tumour).
abstract: BACKGROUND
  Aggressive fibromatosis (desmoid tumour) is a locally invasive tumour caused by mutations resulting in β-catenin protein stabilisation. Apc1638N mice are predisposed to developing aggressive fibromatosis tumours, and male mice develop greater numbers of tumours than female mice, suggesting a role for androgens in this tumour type.
  
  
  METHODS
  Human aggressive fibromatosis tumours were examined for the expression of the androgen receptor, and primary human tumour cell cultures were treated with testosterone. Orchidectomised Apc1638N mice were investigated for the development of tumours, and were treated with testosterone to study the effect of tumour formation and the level of β-catenin.
  
  
  RESULTS
  Androgen receptors are universally expressed in human aggressive fibromatosis tumours. Testosterone increased the proliferation rate and β-catenin protein level in a dose-dependent manner in human aggressive fibromatosis tumours. Orchiectomy reduced the number and size of tumours that formed in male Apc1638N mice to a similar level as observed in female mice. Testosterone treatment increased the number of tumours that formed in orchidectomised male mice, and resulted in a marked increase in β-catenin protein levels.
  
  
  CONCLUSIONS
  Testosterone regulates β-catenin protein level and proliferation rate in this mesenchymal tumour. This work identifies the therapeutic use of testosterone blockade in aggressive fibromatosis as an area for further investigation.
authors.affiliation: Program in Developmental and Stem Cell Biology, Hospital for Sick Children, Toronto Medical Discovery Tower, 101 College Street, Toronto, ON, Canada M5G 1L7.
authors.forename: H
authors.initials: H
authors.lastname: Hong
authors.forename: P
authors.initials: P
authors.lastname: Nadesan
authors.forename: R
authors.initials: R
authors.lastname: Poon
authors.forename: B A
authors.initials: BA
authors.lastname: Alman
mesh_terms: D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects*; D005260:Female; D018222:Desmoid Tumors / Q000378:metabolism* / Q000473:pathology*; D015972:Gene Expression Regulation, Neoplastic; D017491:Genes, APC; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009154:Mutation; D009919:Orchiectomy; D012313:RNA / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013739:Testosterone / Q000009:adverse effects* / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D051176:beta Catenin / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*
chemical_list: D051176:beta Catenin; D013739:Testosterone; D012313:RNA