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Y. S. Yu, J. Kim, J. Kim, K. Park, K.-W. Kim; Neurotrophin Receptors, Trka and Trkb, in Retinoblastoma Are Differentially Expressed Depending on the Cellular Differentiation. Invest. Ophthalmol. Vis. Sci. 2009;50(13):1689.
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© ARVO (1962-2015); The Authors (2016-present)
To investigate whether the differential expression of neurotrophin receptors, TrkA and TrkB, is closely related to the differentiation of retinoblastoma cells
With the treatment of nerve growth factor (NGF), TrkA and TrkB expression were evaluated by RT-PCR and Western blotting in Y79 and SNUOT-Rb1 retiniblastoma cells. To induce the experimental animal models of retinoblastoma, retiniblastoma cells were injected into the intravitreal cavity of nude mice, and enucleation was performed 4 weeks later. Immunohistochemistry for TrkA and TrkB was performed which was merged with Ki67, nm23, or TUNEL. With treatment of retinoic acid, Western blotting for TrkA, TrkB, Erk 1/2 and phosphor-Erk 1/2, and immunocytochemistry for Trk A were performed in retinoblastoma cells.
While retinoblastoma cells expressed TrkA as well as TrkB, their growth rates were not influenced by addition of NGF to the culture medium. In experimental animal models of retinoblastoma, TrkA expression was primarily detected in more differentiated area with high nm23 immunoreactivity, whereas TrkB expression was apparent in more proliferative area with high Ki67 immunoreactivity. With retinoic acid- induced differentiation of retinoblastoma cells, TrkA expression significantly increased, whereas TrkB significantly decreased. Differential expression of TrkA and TrkB with differentiation of retinoblastoma cells was mediated by ERK 1/2 activation, which was confirmed through immunocytochemistry of TrkA.
Our results suggest that differential expression of TrkA and TrkB could be a prognostic factor to reflect biological features of retinoblastoma cells and regulation of neurotrophin receptors could allow a new approach to the treatment of patients with retinoblastoma.
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