Prostate cancer (PCa), the most common non-skin cancer in men, is a worldwide health concern.
Treatment options for aggressive PCa are limited to androgen deprivation therapies (ADT), which are ineffective, with robust diagnostic options also being limited. The prostate specific antigen (PSA) test, for instance, is subject to high levels of false positive results and cannot distinguish between cancer confined to the prostate and aggressive metastatic cancer. As such, additional therapeutic and diagnostic options are urgently required. In recent years, a clear association between activins and prostate cancer has become evident. Activins are members of the TGF-β superfamily and are responsible for a plethora of physiological processes, including cell proliferation, apoptosis, immune surveillance, embryonic development, and follicle stimulating hormone (FSH) regulation. Activin A normally inhibits cancer development and progression, however, cancer cell growth in high-grade PCa is not inhibited by this protein. The mechanism for this apparent acquired capability to resist activin A-mediated growth inhibition is currently not well understood. Thus, the aim of this review is to analyse the role of activin A in PCa progression and to present mechanisms by which transformed cells may escape its effects. The overarching hypothesis is that insensitivity to the growth inhibitory effects of activin A is an acquired capability in PCa progression. Therefore, local and genetic elements that may be responsible for this change in cellular sensitivity to activin A during cancer progression will be highlighted with a view to identifying potential diagnostic or therapeutic targets.
Written by:
Ottley E, Gold E. Are you the author?
Department of Anatomy, University of Otago, Dunedin, New Zealand.
Reference: Cytokine Growth Factor Rev. 2012 Jun;23(3):119-25.
doi: 10.1016/j.cytogfr.2012.04.004
PubMed Abstract
PMID: 22579070
UroToday.com Investigative Urology Section