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Bassel Nazha, Emilia Antecka, Bruno F. Fernandes, Shawn C. Maloney, Maria Eugenia Orellana, Miguel N. Burnier, Jr.; Investigation Of N-CoR Localization And Prognostic Value In Human Retinoblastoma. Invest. Ophthalmol. Vis. Sci. 2011;52(14):2107.
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Nuclear Receptor Corepressor (N-CoR) is a protein complex with diverse functions in development, inflammation and metabolism. Its histone deacetylase, HDAC3, represses the transcription of target genes. N-CoR misregulation is involved in cancer and can be manifested by aberrant subcellular localizations. In colorectal carcinoma, N-CoR was shown to have aberrant cytoplasmic localization, contributing to the transcriptional derepression and tumor progression. In breast cancer, its levels were shown to have a prognostic value. The objective of this study is to investigate the localization and prognostic value of N-CoR in retinoblastoma.
Immunohistochemistry was performed using the Ventana BenchMark fully automated machine. Paraffin embedded, formalin fixed eye sections from 43 retinoblastoma cases and a retinoblastoma cell line (WERY-1) were stained with rabbit polyclonal anti-NCoR1 H76 antibody(1:50 dilutions, Novus Biologicals). Sections of breast cancer were used as positive control. Percentage and intensity of staining were classified from 0 to 3. Student T-test was used to test for differences and p<0.05 was considered to be significant.
In the normal retina, the Inner Nuclear Layer (INL) stained more strongly than the Outer Nuclear Layer (ONL). Even though the tumor cells also showed a predominantly nuclear staining, the cytoplasm of tumor cells showed an increased N-CoR expression when compared to Inner Plexiform Layer (IPL) (p=0.0016) and Outer Plexiform Layer (OPL) (p<0.001). Sparse tumor cells were even noted to have a stronger N-CoR cytoplasmic than nuclear expression. This was also the case in the retinoblastoma cell line where N-CoR was mainly localized in the cytoplasm. Cytoplasmic and nuclear levels of N-CoR did not correlate with demographic and histopathological prognostic features.
We found a higher cytoplasmic expression of N-CoR in retinoblastoma specimens, and the retinoblastoma cell line while a nuclear localization in the normal retina. The localization of N-CoR in the tumor cells is the opposite of their normal counterpart. The increased cytoplasmic localization of N-CoR in retinoblastoma cells may contribute to tumor development by preventing N-CoR’s transcriptional repressive effects in the nucleus.
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