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Elevated level of inhibin-? subunit is pro-tumourigenic and pro-metastatic and associated with extracapsular spread in advanced prostate cancer

Abstract

The biological function of inhibin-alpha subunit (INHalpha) in prostate cancer (PCa) is currently unclear. A recent study associated elevated levels of INHalpha in PCa patients with a higher risk of recurrence. This prompted us to use clinical specimens and functional studies to investigate the pro-tumourigenic and pro-metastatic function of INHalpha. We conducted a cross-sectional study to determine a link between INHalpha expression and a number of clinicopathological parameters including Gleason score, surgical margin, extracapsular spread, lymph node status and vascular endothelial growth factor receptor-3 expression, which are well-established prognostic factors of PCa. In addition, using two human PCa cell lines (LNCaP and PC3) representing androgen-dependent and -independent PCa respectively, we investigated the biological function of elevated levels of INHalpha in advanced cancer. Elevated expression of INHalpha in primary PCa tissues showed a higher risk of PCa patients being positive for clinicopathological parameters outlined above. Over-expressing INHalpha in LNCaP and PC3 cells demonstrated two different and cell-type-specific responses. INHalpha-positive LNCaP demonstrated reduced tumour growth whereas INHalpha-positive PC3 cells demonstrated increased tumour growth and metastasis through the process of lymphangiogenesis. This study is the first to demonstrate a pro-tumourigenic and pro-metastatic function for INHalpha associated with androgen-independent stage of metastatic prostate disease. Our results also suggest that INHalpha expression in the primary prostate tumour can be used as a predictive factor for prognosis of PCa.

Type Journal
ISBN 1532-1827 (Electronic)
Authors Balanathan, P.; Williams, E.D.; Wang, H.; Pedesen, J.S.; Horvath, L.G.; Achen, M.G.; Stacker, S.A.; Risbridger, G.P.
Responsible Garvan Author Prof Lisa Horvath
Publisher Name BRITISH JOURNAL OF CANCER
Published Date 2009-06-01
Published Volume 100
Published Issue 11
Published Pages 1784-1793
Status Published in-print
DOI 10.1038/sj.bjc.6605089
URL link to publisher's version http://www.nature.com/bjc/journal/v100/n11/full/6605089a.html
OpenAccess link to author's accepted manuscript version https://publications.gimr.garvan.org.au/open-access/10156