Journal
CELL DEATH AND DIFFERENTIATION
Volume 19, Issue 1, Pages 170-179Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/cdd.2011.83
Keywords
sialidase; prostate cancer; androgen receptor; EGR-1; PSA
Categories
Funding
- CREST of Japan Science and Technology Agency
- Ministry of Education, Culture, Sports, Science and Technology of Japan [20013047]
- Grants-in-Aid for Scientific Research [21570122, 20013047, 22118002, 23592471, 22118001, 22659248, 23249051] Funding Source: KAKEN
Ask authors/readers for more resources
Prostate cancers generally become androgen-independent and resistant to hormone therapy with progression. To understand the underlying mechanisms and facilitate the development of novel treatments for androgen-independent prostate cancer, we have investigated plasma membrane-associated sialidase (NEU3), the key enzyme for ganglioside hydrolysis participating in transmembrane signaling. We have discovered NEU3 to be upregulated in human prostate cancer compared with non-cancerous tissue, correlating with the Gleason score. NEU3 silencing with siRNA in prostate cancer PC-3 and LNCaP cells resulted in increased expression of differentiation markers and in cell apoptosis, but decrease in Bcl-2 as well as a progression-related transcription factor, early growth response gene (EGR-1). In androgen-sensitive LNCaP cells, forced overexpression of NEU3 significantly induced expression of EGR-1, androgen receptor (AR) and PSA both with and without androgen, the cells becoming sensitive to androgen. The NEU3-mediated induction was abrogated by inhibitors for PI-3 kinase and MAP kinase and more specifically by their silencing in the absence of androgen, being confirmed by increased phosphorylation of AKT and ERK1/2 in NEU3 overexpressing cells. NEU3 siRNA introduction caused reduction of cell growth of an androgen-independent PC-3 cells in culture and of transplanted tumors in nude mice. These data suggest that NEU3 regulates tumor progression through AR signaling, and thus be a potential tool for diagnosis and therapy of androgen-independent prostate cancer. Cell Death and Differentiation (2012) 19, 170-179; doi:10.1038/cdd.2011.83; published online 17 June 2011
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available