Bone Morphogenetic Protein-10 suppresses the growth and aggressiveness of prostate cancer cells through a Smad independent pathway

Ye, Lin ORCID: https://orcid.org/0000-0002-0303-2409, Kynaston, Howard ORCID: https://orcid.org/0000-0003-1902-9930 and Jiang, Wen Guo ORCID: https://orcid.org/0000-0002-3283-1111 2009. Bone Morphogenetic Protein-10 suppresses the growth and aggressiveness of prostate cancer cells through a Smad independent pathway. The Journal of Urology 181 (6) , pp. 2749-2759. 10.1016/j.juro.2009.01.098

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Abstract

Purpose BMPs have been implicated in the development of bone metastasis in prostatecancer. We investigated the role of BMP-10 in prostatecancer and prostatecancercells. Materials and Methods BMP-10 expression was examined in human prostate tissue and prostatecancercell lines. BMP-10 was experimentally over expressed in human prostatecancercells. The influence of BMP-10 on the biological behavior of prostatecancercells was then investigated in in vitro studies. Results BMP-10 expression was decreased or absent in prostate tumors, particularly in higher grade foci. Forced BMP-10 over expression in prostatecancercells decreased in vitro growth, cell matrix adhesion, invasion and migration. Furthermore, BMP-10 induced apoptosis in prostatecancercells through aSmadindependentpathway, in which the 2 downstream candidates of BMP receptors XIAP (ILP) and ERK1/2 were activated. Interestingly the failure of BMP-10 to activate BMP receptor-II and the Smads in WT cells was due to the expression of BMP receptor-IB, which acted as a negative regulator of BMP receptor-II mediated Smad dependent signaling. Conclusions BMP-10 inhibits the growth of prostatecancercells due largely to induced apoptosis via Smadindependent signaling in which XIAP and ERK1/2 are involved. BMP-10 can also prevent prostatecancercell migration and invasiveness. This suggests that BMP-10 may function as a tumor suppressor and apoptosis regulator for prostatecancer.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine
Subjects:	R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer)
Uncontrolled Keywords:	prostate; prostatic neoplasms; bone morphogenetic proteins; apoptosis; neoplasm invasiveness
Publisher:	Elsevier
ISSN:	0022-5347
Last Modified:	19 Oct 2022 10:41
URI:	https://orca.cardiff.ac.uk/id/eprint/25210

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