Abstract
Purpose: :
To reporet BMI-1 expression and its clinicopathological correlation in 36 archived human retinoblastomas by immunohistochemistry
Methods: :
Retinoblastoma Y79 cells were transfected to over-express or specific knockdown human BMI-1 and collected for cell proliferation and apoptosis analyses, flow cytometry and gene expression study using reverse-transcription polymerase chain reaction and western blotting.
Results: :
Our results showed that BMI-1 was widely expressed in retinoblastomas. Notably, high BMI-1 expression was restricted to their undifferentiated counterparts and tumors with extraocular invasion. In Y79 cells, ectopic BMI-1 expression stimulated proliferation and suppressed apoptosis, and this was coupled with down-regulated p14ARF and p16INK4 expressions and upregulated proliferating cell nuclear antigen, cyclin D1 and D2 expressions. In contrast, silencing BMI-1 could efficiently reverse these expression changes. We also observed that BMI-1 increased Chx10 expression, but not other retina development-related genes, nestin and neurofilament M. Our results showed that BMI-1 expression was associated with the undifferentiation and aggressiveness of retinoblastomas and it might play imporant roles in maintaining retinoblastoma cell properties with regards to growth and proliferation.
Conclusions: :
BMI-1 could be developed as a promising prognostic marker and therapeutic target of retinoblastomas.
Keywords: retinoblastoma • pathobiology