Testosterone regulates cell proliferation in aggressive fibromatosis (desmoid tumour)

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 fo...

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Bibliographic Details
Published in:British journal of cancer 2011-04, Vol.104 (9), p.1452
Main Authors: Hong, H, Nadesan, P, Poon, R, Alman, B A
Format: Article
Language:English
Subjects:
Androgens
Animals
beta Catenin - drug effects
beta Catenin - genetics
beta Catenin - metabolism
Cancer research
Cell culture
Cell growth
Cell Proliferation - drug effects
Connective tissue diseases
Female
Fibromatosis, Aggressive - metabolism
Fibromatosis, Aggressive - pathology
Gene Expression Regulation, Neoplastic
Genes
Genes, APC
Genetic Predisposition to Disease
Humans
Ligands
Male
Medical research
Mice
Mice, Inbred Strains
Mutation
Orchiectomy
Proteins
Reverse Transcriptase Polymerase Chain Reaction
RNA - metabolism
Testosterone
Testosterone - adverse effects
Testosterone - metabolism
Tumor Cells, Cultured
Tumors
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Summary: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. 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. 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. 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.
ISSN:0007-0920
1532-1827
DOI:10.1038/bjc.2011.107