Abstract
Purpose: :
To elucidate the differential expression patterns of metalloproteinases (MMPs) involved in retinoblstoma cell proliferation and differentiation.
Methods: :
The new human retinoblastoma cell line SNUOT-Rb1 and Y79 were treated with 5 ng/ml recombinant human bFGF for proliferation and serum-deprivation for differentiation for 48h. The expression patterns of MMP-2,-9, and -14; tissue inhibitor of MMPs (TIMPs)-1 and -2; Ki-67 and nm23 were analyzed by RT-PCR. The regulation of protein was studied by western blot analysis. Immnunohistochemistry for MMP-2, 9, and 14; Ki-67 and nm23 assessed in human retinoblastoma tissues.
Results: :
In proliferation SNUOT-Rb1 and Y79 cells, the expression level of MMP-9 was elevated. In contrast, differentiation cells exhibited decreased MMP-9 levels and increased MMP-2 and -14 levels. Moreover, TIMP-1 and -2 expression levels did not change in both proliferation and differentiation. In proliferation, the ERK activation was more increased than Akt acrivation. The ERK activation was inhibited by inhibitor of MMP-9 in cell proliferation.
Conclusions: :
These results suggest that MMP-9 activity was increased during retinoblastoma proliferation, where MMP-2 and MMP-14 activity was elevated during retinoblastoma differentiation. We conclude that MMPs are involved in cell proliferation and differentiation exhibit different patterns of MMP-9 and MMP-2 activity.
Keywords: retinoblastoma • proliferation • differentiation