Abstract
Purpose:
To explore the functional significance of human papillomaviruses (HPVs) on human uveal melanoma cells.
Methods:
mRNA and protein expression of HPV subtypes on human uveal melanoma (UM) cell lines VUP, SP6.5, OCM1, OM431 and a normal human retinal pigment cell line, ARPE-19 were examined using HPV genotyping DNA chip or western blot, respectively. mRNA expression of HPV subtype in confirmed UM cells was knocked down with RNA interference (RNAi) . Cell cycle and apoptosis of HPV koncked down UM cells were determined by flow cytometry. The expression of phosphorylated p53, phosphorylated Rb, p21, and cyclin D1 was detected by western blot in HPV downregulated UM cells.
Results:
VUP cell lines were HPV 18 positive, while other cell lines were negative for the detected HPV subtypes. HPV 18 E6/E7 oncoproteins in UM and ARPE-19 cells were positively expressed. Downregulation of HPV 18 E6/E7 oncoproteins by siRNA decreased viability and led to disturbed cell cycle distribution. p53 and Rb pathways were activated by E6/E7-specific RNAi in VUP cells.
Conclusions:
HPV is possibly involved in the carcigenesis of some UM cells, and provide a potential target in dealing wiht UM.
Keywords: 426 apoptosis/cell death •
624 oncology •
637 pathology: experimental