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Vikas Khetan, Gopal Lingam, Ramya S, Nalini Venkatesan, Subramaniam Krishnakumar; A Preliminary Report On The Expression Of Prame In Retinoblastoma: Its Association With Drug Resistance. Invest. Ophthalmol. Vis. Sci. 2011;52(14):2108.
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Gene expression profile of chemo-treated retinoblastoma tumor compared with that of a tumor enucleated without prior chemotherapy revealed PRAME, (Preferentially Expressed Antigen of Melanoma) to be upregulated. (Invest Ophthalmol Vis Sci 2010;51: E-Abstract 2063). PRAME is also expressed at high levels in haematological malignancies and solid tumours. PRAME has been implicated in multidrug resistance in childhood cancers. In this study we report expression of PRAME in retinoblastoma and its association with drug resistance. We investigated the relationship between PRAME over expression and the expression of MDR-related genes.
PRAME expression was studied using Immunohistochemistry(16 Retinoblastoma tumors), Quantitative Real Time PCR,(7 Retinoblastoma tumors) and Flow cytometry (5 RB tumors). The association of PRAME overexpression in retinoblastoma cell line(y79) with Drug resistance was studied using Quantitative Real Time PCR and cell viability assay.
In Immunohistochemistry, out of 16 tumors, PRAME expression was negative in 1 tumor (0.06%), less expression in 3 tumors (20%), Moderate expression in 5 tumors (33.3%), higher expression in 7 tumors (46.6%). In qRT-PCR, 57% of tumors showed upregulation of PRAME expression in retinoblastoma. There is no statistical significant correlation with respect to chemotherapy in retinoblastoma tumors. The relationship between PRAME over expression (transient) and the expression of MDR-related genes especially MRP1 revealed only 2.2 fold increase .The cell viability assay in the presence of Carboplatin drug at concentrations ranging from 25 mg/ml to 45 mg/ml revealed no significant change in the IC50 (30 mg/ml) compared to the untransfected Y79 cells. This interprets PRAME may not play a significant role in the drug resistance of Retinoblastoma.
Our results suggest that PRAME may not play a role in drug resistance in retinoblastoma unlike other childhood cancers . The physiological functions of PRAME in normal and tumour cells are unknown, although a role in the regulation of retinoic acid signalling has been proposed. Earlier we showed that Cellular retinoic acid binding protein II (CRABP-II) was highly upregulated and CRABP-1 was downregulated in the retinoblastoma tumors compared to the retina. (Invest Ophthalmol Vis Sci 2009;50: E-Abstract 2042).Thus further studies are needed to understand the role of PRAME in retinoblastoma.
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