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M. W. Wilson, C. H. Fraga, C. Rodriguez-Galindo, N. Hagedorn, C. F. Stewart; Pregnane X Receptor Expression in Untreated and Treated Retinoblastoma. Invest. Ophthalmol. Vis. Sci. 2007;48(13):1606.
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The Pregnane X Receptor (PXR) is an orphan nucleotide receptor that induces the expression of select ATP-binding cassette (ABC)/ multidrug resistance proteins such as multidrug resistance-1/ P-glycoprotein (MDR1/P-gp), multidrug resistant protein 1 (MRP1/ABCC1), multidrug resistant protein 2 (MRP2/ABCC2), multidrug resistant protein 4 (MRP4/ABCC4) and breast cancer resistance protein (BCRP/ABCG2). The purpose of our study is to compare the expression of PXR in retinoblastoma tumors among eyes treated with primary enucleation and eyes treated with primary systemic chemotherapy and/or external beam radiation (EBRT) and to correlate these findings with the expression of the multidrug resistance proteins.
A tissue microarray was constructed with the archival specimens from 50 enucleated eyes. Using standard immunohistochemical techniques, the tissue microarrays were studied for the expression of PXR and 5 ABC transporters: MDR1, MRP1, MRP2, MRP4 and BCRP.
Of the 50 eyes studied, 37 were primarily enucleated, 5 had been treated with chemotherapy alone, and 8 had been treated with both chemotherapy and EBRT. Results are summarized for each cohort in the table.
Preliminary analysis of our data shows that the majority of both untreated and treated retinoblastoma tumors express PXR. Untreated eyes expressed PXR at rates similar to treated eyes (65% versus 69%). Given the variable expression of the multidrug resistant proteins in the same retinoblastoma tumors, it does not appear that PXR alone accounts for the induction of any specific or particular ABC transporter.
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