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Article

Osteopontin-c mediates the upregulation of androgen responsive genes in LNCaP cells through PI3K/Akt and androgen receptor signaling

  • Authors:
    • Tatiana Martins Tilli
    • Luciana Bueno Ferreira
    • Etel Rodrigues Pereira Gimba
  • View Affiliations / Copyright

    Affiliations: Molecular Carcinogenesis Program, Research Coordination, National Institute of Cancer, Rio de Janeiro 22743-051, Brazil, Institute of Molecular Pathology and Immunology, University of Porto, Porto 4200-465, Portugal
  • Pages: 1845-1850
    |
    Published online on: February 6, 2015
       https://doi.org/10.3892/ol.2015.2939
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Abstract

Androgen receptor (AR) signaling is a key pathway modulating prostate cancer (PCa) progression. Several steps in this pathway have been investigated in order to propose novel treatment strategies for advanced PCa. Total osteopontin (OPN) has been described as a biomarker for PCa, in addition to its role in activating the progression of this tumor. Based on the known effects of the OPNc splice variant on PCa progression, the present study investigated whether this isoform can also modulate AR signaling. In order to test this, an in vitro model was used in which LNCaP cells were cultured in the presence of conditioned medium (CM) secreted by PCa cells overexpressing OPNc (OPNc‑CM). The activation of AR signaling was evaluated by measuring the expression levels of AR‑responsive genes (ARGs) using quantitative polymerase chain reaction and specific oligonucleotides. The data demonstrated that all nine tested ARGs (Fgf8, TMPRSS2, Greb1, Cdk2, Ndrg1, Cdk1, Pmepa1, Psa and Ar) are significantly upregulated in response to OPNc‑CM compared with LNCaP cells cultured in CM secreted by control cells transfected with empty expression vector. The specific involvement of OPNc was demonstrated by depleting OPNc from OPNc‑CM using an anti‑OPNc neutralizing antibody. In addition, by using a phosphoinositide 3-kinase (PI3K)‑specific inhibitor and AR antagonists, such as flutamide and bicalutamide, it was also observed that upregulation of ARGs in response to OPNc‑CM involves PI3K signaling and depends on the AR. In conclusion, these data indicated that OPNc is able to activate AR signaling through the PI3K pathway and the AR. These data further corroborate our previous data, revealing the OPNc splice variant to be a key molecule that is able to modulate key signaling pathways involved in PCa progression.
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Copy and paste a formatted citation
Spandidos Publications style
Tilli TM, Ferreira LB and Gimba ER: Osteopontin-c mediates the upregulation of androgen responsive genes in LNCaP cells through PI3K/Akt and androgen receptor signaling. Oncol Lett 9: 1845-1850, 2015.
APA
Tilli, T.M., Ferreira, L.B., & Gimba, E.R. (2015). Osteopontin-c mediates the upregulation of androgen responsive genes in LNCaP cells through PI3K/Akt and androgen receptor signaling. Oncology Letters, 9, 1845-1850. https://doi.org/10.3892/ol.2015.2939
MLA
Tilli, T. M., Ferreira, L. B., Gimba, E. R."Osteopontin-c mediates the upregulation of androgen responsive genes in LNCaP cells through PI3K/Akt and androgen receptor signaling". Oncology Letters 9.4 (2015): 1845-1850.
Chicago
Tilli, T. M., Ferreira, L. B., Gimba, E. R."Osteopontin-c mediates the upregulation of androgen responsive genes in LNCaP cells through PI3K/Akt and androgen receptor signaling". Oncology Letters 9, no. 4 (2015): 1845-1850. https://doi.org/10.3892/ol.2015.2939
Copy and paste a formatted citation
x
Spandidos Publications style
Tilli TM, Ferreira LB and Gimba ER: Osteopontin-c mediates the upregulation of androgen responsive genes in LNCaP cells through PI3K/Akt and androgen receptor signaling. Oncol Lett 9: 1845-1850, 2015.
APA
Tilli, T.M., Ferreira, L.B., & Gimba, E.R. (2015). Osteopontin-c mediates the upregulation of androgen responsive genes in LNCaP cells through PI3K/Akt and androgen receptor signaling. Oncology Letters, 9, 1845-1850. https://doi.org/10.3892/ol.2015.2939
MLA
Tilli, T. M., Ferreira, L. B., Gimba, E. R."Osteopontin-c mediates the upregulation of androgen responsive genes in LNCaP cells through PI3K/Akt and androgen receptor signaling". Oncology Letters 9.4 (2015): 1845-1850.
Chicago
Tilli, T. M., Ferreira, L. B., Gimba, E. R."Osteopontin-c mediates the upregulation of androgen responsive genes in LNCaP cells through PI3K/Akt and androgen receptor signaling". Oncology Letters 9, no. 4 (2015): 1845-1850. https://doi.org/10.3892/ol.2015.2939
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