Role of B lymphoma Mo-MLV insertion region 1 in the oncogenic behavior of retinoblastomas

• Published in: Molecular vision 2013-03, Vol.19, p.561-574
• Main Authors: Ren, Ruojin, Liu, Weiwei, Huang, Li, Liu, David Tai Li, Choy, Kwong Wai, Shi, Jitong, Zhao, Junyang, Zhao, Bowen, Guan, Ming, Shields, Carol L, Pang, Chi Pui, Li, Bin, Yam, Gary Hin Fai
• Format: Article
• Language: English
• Subjects: Apoptosis - genetics; Cell Differentiation; Cell Line, Tumor; Cell Proliferation; Cell Transformation, Neoplastic - genetics; Cell Transformation, Neoplastic - pathology; Child, Preschool; Demography; Female; Gene Expression Regulation, Neoplastic; Humans; Male; Neoplasm Invasiveness; Polycomb Repressive Complex 1 - genetics; Polycomb Repressive Complex 1 - metabolism; Retinoblastoma - genetics; Retinoblastoma - metabolism; Retinoblastoma - pathology; Spheroids, Cellular - metabolism; Spheroids, Cellular - pathology; Staining and Labeling
• ISSN: 1090-0535

This study investigated the relationship between B lymphoma Mo-MLV insertion region 1 (BMI-1)--a polycomb protein for stem cell self-renewal and proliferation--and the clinicopathological parameters of human retinoblastomas, including differentiation status and retinal tissue invasion, as well as the effects of BMI-1 on retinoblastoma Y79 cells. Thirty-four archived human retinoblastoma samples were recruited for BMI-1 immunohistochemistry. The percentage of BMI-1-expressing cells was scored by independent pathologists and the data were correlated with the clinical features. Y79 cells were transfected to overexpress or specifically inhibit BMI-1 for cell proliferation, propidium iodide cell cycle and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) apoptosis analyses, multicellular sphere formation assay, and gene expression study. BMI-1 was widely expressed in human retinoblastomas. Higher percentages of BMI-1-expressing cells were selectively limited to undifferentiated tumors and those tumors undergoing invasion to the optic nerve and choroid. However, there was no difference in BMI-1 expression in retinoblastoma retinas with or without tumor invasion. In Y79 cells, BMI-1 stimulated cell proliferation and suppressed apoptosis with reduced p14ARF and p16INK4 expression, along with upregulation of proliferating cell nuclear antigens cyclin D1 and D2. In contrast, silencing BMI-1 reversed these changes. It also upregulated CHX10 and Rx, but not other retinal development-related genes, including nestin and neurofilament M. Our work indicates that BMI-1 might render important oncogenic property of retinoblastomas and it could be a therapeutic target for the cancer treatment.