Abstract
Purpose: :
To confirm the expression of tissue factor(TF) in the retinoblastoma cell and to identify intracellular signal pathways down-stream to TF, which is responsible for the proliferation of retinoblastoma cell.
Methods: :
TF expression in Y79 and SNUOT Rb1 cell was proved by Western blot analysis. In a xenograft mouse model of retinoblastoma, the expression pattern of TF and ki67 was determined by immunohistochemistry. Change in the level of TF expression on retinoblastoma cell was evaluated after fibroblast growth factor-2 (FGF-2) treatment. The effect of FGF-2 and tissue factor pathway inhibitor (TFPI) on the retinoblastoma cell proliferation were assessed by MTT assay. Phospholyation status of Akt and ERK1/2 was also analyzed from retinoblastoma cell, which was treated with TFPI.
Results: :
TF is exclusively expressed on actively proliferating subpopulations of retinoblastoma cell in the xenograft mouse model. We found an dose dependant overexpression of TF on the retinoblastoma cell in respond to FGF-2. Retinoblastoma cell proliferation was stimulated by FGF-2, and suppressed by TFPI. Retinoblastoma cell, incubated with bFGF showed increased phosphorylation of both Akt and ERK 1/2. TFPI effectively inhibited Akt phosphorylation, but the level of ERK 1/2 phosphorylation was not influenced by TFPI.
Conclusions: :
Our data suggests that TF expressed on retinoblastoma cell is closely related to retinoblastoma cell proliferation. And TF may exerts this action through the activation of Akt-PI3K pathway, not of ERK 1/2 pathway.
Keywords: retinoblastoma • pathology: experimental • tumors