Bone morphogenetic protein-9 induces apoptosis in prostate cancer cells, the role of prostate apoptosis response-4

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 2008. Bone morphogenetic protein-9 induces apoptosis in prostate cancer cells, the role of prostate apoptosis response-4. Molecular Cancer Research 6 (10) , pp. 1594-1606. 10.1158/1541-7786.MCR-08-0171

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Abstract

Bone morphogenetic proteins (BMP) have been implicated in the development of bone metastases in prostate cancer. In this study, we investigated the role which BMP-9 played in prostate cancer and found that the expression of BMP-9 was decreased or absent in prostate cancer, particularly in the foci of higher grade disease. We further investigated the influence of BMP-9 on the biological behaviors of prostate cancer cells. The forced overexpression of BMP-9 prevented the in vitro growth, cell-matrix adhesion, invasion, and migration of prostate cancer cells. We also elucidated that BMP-9 induced apoptosis in PC-3 cells through the up-regulation of prostate apoptosis response-4. Among the receptors which have been implicated in the signaling of BMP-9, BMPR-IB and BMPR-II have also been implicated in the development and progression of prostate cancer. Knockdown of BMPR-IB or BMPR-II using respective hammerhead ribozyme transgenes could promote cell growth in vitro. We also found that BMPR-II is indispensable for the Smad-dependent signal transduction by BMP-9 in PC-3 cells, in which Smad-1 was phosphorylated and translocated from the cytoplasm into the nuclei. Taken together, BMP-9 inhibits the growth of prostate cancer cells due to the induced apoptosis, which is related to an up-regulation of prostate apoptosis response-4 through a Smad-dependent pathway. BMP-9 could also prevent the migration and invasiveness of prostate cancer. This suggests that BMP-9 may function as a tumor suppressor and apoptosis regulator in prostate cancer.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine
Subjects:	R Medicine > R Medicine (General) R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer)
Uncontrolled Keywords:	Bone morphogenetic protein-9; Prostate apoptosis response-4; Prostate cancer
Publisher:	American Association for Cancer Research
ISSN:	1541-7786
Last Modified:	20 Oct 2022 08:13
URI:	https://orca.cardiff.ac.uk/id/eprint/27650

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