Henry C. Witelson Ocular Pathology Laboratory, Department of Ophthalmology, McGill University, Montreal, Que., Canada.
Ophthalmic Res. 2013;49(4):171-6. doi: 10.1159/000345535. Epub 2013 Jan 3.
BACKGROUND/AIMS: Nuclear receptor corepressor 1 (NCoR1) is a protein complex with diverse functions in development and tumorigenesis. We investigated the pattern of expression and histopathological correlation of NCoR1 in 41 retinoblastoma tumor samples, 1 retinoblastoma cell line (WERI-Rb-1) and human retinal progenitor cells (hRPCs).
Tissue sections from 41 retinoblastoma cases, the retinoblastoma cell line WERI-Rb-1 and hRPCs were stained with rabbit polyclonal anti-NCoR1 H76 antibody. Percentage and intensity of staining were classified by an ocular pathologist from 0 to 3. The paired t test was used to test for differences.
In the nonneoplastic retina, NCoR1 was expressed mainly in cell nuclei. The retinoblastoma tumor cells similarly had nuclear NCoR1 but also had a higher level of cytoplasmic NCoR1 expression compared to all 3 normal retinal cell layers (p < 0.002). In contrast to the normal retina, NCoR1 was mainly expressed in the cytoplasm of the proliferating WERI-Rb-1 cells. This cytoplasmic expression pattern was also seen in the undifferentiated hRPCs.
The aberrant cytoplasmic expression of NCoR1 in retinoblastoma appears to be associated with the proliferative and/or dedifferentiated properties of retinoblastoma. Further investigation into the role of NCoR1 in retinoblastoma may provide insight into how therapeutically inhibiting its nucleocytoplasmic shuttling may affect retinoblastoma tumor biology.
背景/目的：核受体共抑制因子 1（NCoR1）是一种具有多种功能的蛋白复合物，在发育和肿瘤发生中具有重要作用。我们研究了 NCoR1 在 41 例视网膜母细胞瘤肿瘤样本、1 株视网膜母细胞瘤细胞系（WERI-Rb-1）和人视网膜祖细胞（hRPCs）中的表达模式和组织病理学相关性。
用兔多克隆抗 NCoR1 H76 抗体对 41 例视网膜母细胞瘤病例、WERI-Rb-1 视网膜母细胞瘤细胞系和 hRPCs 的组织切片进行染色。由眼病理学家将染色强度和染色百分比分别分为 0-3 级。采用配对 t 检验比较差异。
在非肿瘤性视网膜中，NCoR1 主要表达于细胞核。与所有 3 种正常视网膜细胞层相比，视网膜母细胞瘤肿瘤细胞同样具有核内 NCoR1，但也具有更高水平的细胞质 NCoR1 表达（p<0.002）。与正常视网膜不同，NCoR1 主要表达于增殖的 WERI-Rb-1 细胞的细胞质中。这种细胞质表达模式也见于未分化的 hRPCs。
视网膜母细胞瘤中 NCoR1 的异常细胞质表达似乎与视网膜母细胞瘤的增殖和/或去分化特性有关。进一步研究 NCoR1 在视网膜母细胞瘤中的作用可能有助于了解如何通过抑制其核质穿梭来影响视网膜母细胞瘤的肿瘤生物学。
