TGF-beta signalling and immunity in prostate tumourigenesis.
BACKGROUND
The TGF-beta's are pleiotropic cytokines that regulate multiple cellular functions. Their role in the prostate is important for normal prostate development and also in prostate tumourigenesis.


METHODS
The interactions TGF-beta-mediated signalling has with maintaining prostate health, as well as its role in prostate tumourigenesis and prostate tumour immune evasion, with emphasis on how a breakdown in these interactions may influence disease progression.


RESULTS
That TGF-beta influences normal prostate growth and differentiation by regulating the balance between epithelial cell proliferation and apoptosis, and involving the androgen receptor pathway. That TGF-beta protects and maintains prostate stem cells and a review of the contrasting role TGF-beta has in prostate tumourigenesis and tumour development, where TGF-beta acts as a tumour suppressor and then switches roles to become a tumour promoter, and creates a local immunosuppressive niche leading to systemic tumour tolerance.


CONCLUSIONS
TGF-beta signalling in prostate cancer is a valid target for the treatment of this disease; however any therapeutic regimen will require an understanding of all aspects of the TGF-beta-signalling nexus, otherwise by the very pleiotrophic nature of TGF-beta, limited clinical benefits may result.
Diener
Kerrilyn R
KR
Hanson Institute, Experimental Therapeutics Laboratory, Adelaide, SA 5000, Australia.
Need
Eleanor F
EF
Buchanan
Grant
G
Hayball
John D
JD
D000726:Androgen Antagonists / Q000494:pharmacology; D000818:Animals; D006801:Humans; D008213:Lymphocyte Activation; D008297:Male; D011471:Prostatic Neoplasms / Q000209:etiology* / Q000276:immunology*; D011509:Proteoglycans / Q000502:physiology; D011944:Receptors, Androgen / Q000502:physiology; D018125:Receptors, Transforming Growth Factor beta / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology*; D013234:Stem Cells / Q000502:physiology; D013601:T-Lymphocytes / Q000276:immunology; D016212:Transforming Growth Factor beta / Q000502:physiology*; D019139:Tumor Escape
D000726:Androgen Antagonists; D011509:Proteoglycans; D011944:Receptors, Androgen; D018125:Receptors, Transforming Growth Factor beta; D016212:Transforming Growth Factor beta; C071736:betaglycan