Session 1G: Foxi3 Ablation Retards Bone Derived Prostate Cancer Cell Growth

Session Number

Session 1G : 4th Presentation

Advisor(s)

Jacqueline Jones, Troy University

Location

Room A117

Start Date

28-4-2017 8:30 AM

End Date

28-4-2017 9:45 AM

Abstract

Prostate cancer is the abnormal growth of cells in the prostate gland and studies have shown that 100% of men that die from prostate cancer have bone involvement. Of the many cells resident in the bone, myeloid cells secrete various soluble factors that contribute to the high turnover rate of cells and molecular processes of bone development. Of particular interest, Foxi3, a forkhead family transcription factor is critical in bone development and embryogenesis. However, its role in prostate cancer, has not been explored. Therefore, we hypothesized that Foxi3 is a key factor in promoting prostate cancer progression to the bone and its expression is modulated by FGF8. To investigate the clinical role of Foxi3 and study the effect of FGF8 on Foxi3 high expressing cells (PC3 and C42b), we analysed its expression and function in human prostate cancer tissue and cell lines with or without FGF8 treatment. A significant increase in Foxi3 expression as cancer becomes more aggressive is identified in human specimens (p<0.01). Immunohistochemical analysis demonstrated a significant association of Foxi3 expression with tumor grade (p<0.05) and pathology (p<0.01). Further, C42b cells treated with FGF8 presented an 80- fold increase in Foxi3 expression and a significant increase in migration and proliferation rate (p<0.001). Interestingly, Foxi3 inhibition (si-RNA-Foxi3) in PC3 and C42b cells, significantly decreased cell proliferation and migration (p<0.01), even in the presence of FGF8. Together, our findings illustrate a synergistic oncogenic role of Foxi3 and FGF8 in promoting prostate cancer bone metastases.

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Apr 28th, 8:30 AM Apr 28th, 9:45 AM

Session 1G: Foxi3 Ablation Retards Bone Derived Prostate Cancer Cell Growth

Room A117

Prostate cancer is the abnormal growth of cells in the prostate gland and studies have shown that 100% of men that die from prostate cancer have bone involvement. Of the many cells resident in the bone, myeloid cells secrete various soluble factors that contribute to the high turnover rate of cells and molecular processes of bone development. Of particular interest, Foxi3, a forkhead family transcription factor is critical in bone development and embryogenesis. However, its role in prostate cancer, has not been explored. Therefore, we hypothesized that Foxi3 is a key factor in promoting prostate cancer progression to the bone and its expression is modulated by FGF8. To investigate the clinical role of Foxi3 and study the effect of FGF8 on Foxi3 high expressing cells (PC3 and C42b), we analysed its expression and function in human prostate cancer tissue and cell lines with or without FGF8 treatment. A significant increase in Foxi3 expression as cancer becomes more aggressive is identified in human specimens (p<0.01). Immunohistochemical analysis demonstrated a significant association of Foxi3 expression with tumor grade (p<0.05) and pathology (p<0.01). Further, C42b cells treated with FGF8 presented an 80- fold increase in Foxi3 expression and a significant increase in migration and proliferation rate (p<0.001). Interestingly, Foxi3 inhibition (si-RNA-Foxi3) in PC3 and C42b cells, significantly decreased cell proliferation and migration (p<0.01), even in the presence of FGF8. Together, our findings illustrate a synergistic oncogenic role of Foxi3 and FGF8 in promoting prostate cancer bone metastases.