Reference : Both osteopontin-c and osteopontin-b splicing isoforms exert pro-tumorigenic roles in pr...
Scientific journals : Article
Life sciences : Biochemistry, biophysics & molecular biology
Human health sciences : Oncology
http://hdl.handle.net/2268/126343
Both osteopontin-c and osteopontin-b splicing isoforms exert pro-tumorigenic roles in prostate cancer cells.
English
Tilli, T. M. [> >]
Mello, K. D. [> >]
Ferreira, L. B. [> >]
Matos, A. R. [> >]
Accioly, M. T. [> >]
Faria, P. A. [> >]
Bellahcene, Akeila mailto [Université de Liège - ULg > Département des sciences biomédicales et précliniques > GIGA-R : Labo de recherche sur les métastases >]
Castronovo, Vincenzo mailto [Université de Liège - ULg > Département des sciences biomédicales et précliniques > Biologie générale et cellulaire >]
Gimba, E. R. [> >]
2012
Prostate
Wiley Liss
Yes (verified by ORBi)
International
0270-4137
1097-0045
New York
NY
[en] osteopontin ; splicing isoforms ; alternative splicing ; prostate cancer
[en] BACKGROUND: Alternative splicing of the osteopontin (opn, spp1) gene generates three protein splicing isoforms (OPN-SI), designated as OPNa, OPNb, and OPNc, which have demonstrated specific roles in different tumor models. This work aims to investigate the roles of each OPN-SI in prostate cancer (PCa) progression by using in vivo and in vitro functional assays. METHODS: The expression levels of OPN-SI in prostate cell lines were analyzed by qRT-PCR. PC-3 was stably transfected with expression vectors containing OPNa, OPNb, and OPNc, as well as empty vector controls. PC-3 cells overexpressing each construct were analyzed for in vivo tumor growth and in relation to different aspects mimicking tumor progression, such as cell proliferation, migration, invasion, and soft agar colony formation. RESULTS: OPN-SI are overexpressed in PCa as compared to non-tumoral prostate cell lines. OPNc and OPNb overexpressing cells significantly activated enhanced xenograft tumor growth and PC-3 proliferation, migration, invasion, and soft agar colony formation, as well as the expression of MMP-2, MMP-9, and VEGF. These isoforms also support sustained proliferative survival. We found that both OPNc and OPNb pro-tumorigenic roles are mainly mediated through PI3K signaling. Inhibition of this pathway by using LY294002 specifically inhibited tumor progression features evoked by OPNc and OPNb overexpression. CONCLUSIONS: Our data provide evidence that both OPNc and OPNb splicing isoforms promote distinct aspects of PCa progression by inducing PI3K signaling. These data give support to strategies aiming to downregulate OPNc and OPNb expression as an approach to inhibit PCa progression. Prostate (c) 2012 Wiley Periodicals, Inc.
Giga-Cancer
http://hdl.handle.net/2268/126343
10.1002/pros.22523
Copyright (c) 2012 Wiley Periodicals, Inc.

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