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Geeta K. Vemuganti, Murali M S Balla, Imran Khan, Ravi Kiran R. Kalathur, Rohini Nair, Chitra Kannabiran, Santosh G. Honavar, Kondaiah Paturu; Fetal Neural Stem Cell Signaling in Human Retinoblastoma Tumors. Invest. Ophthalmol. Vis. Sci. 2011;52(14):1594.
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© ARVO (1962-2015); The Authors (2016-present)
In accordance with the evidence obtained from other tumors, Retinoblastoma (Rb) is known to harbor cancer stem cell that could possibly contribute to chemoresistance. We herein present the gene expression pattern of freshly isolated tumor cells with special emphasis on self-renewal signaling pathways common to fetal stem cells.
Freshly isolated tumor cells (n=11) were obtained from enucleated eye balls diagnosed for Rb. The micro array assays was performed on the tumor samples using normal appearing retina of the enucleated eyes with Rb as controls. (n=1). The results thus obtained were validated in comparison to normal retinas (n=2), using real-time pcr for expression of N-Myc, HMGA2, LIN-28b and activin receptor 1C (ACVR1C). Furthermore immunoreactivity for AVR1C was evaluated on tissue sections, with an attempt to correlate with varying degree of differentiation and high risk factors.
Of the 10,457 deregulated genes (p ≤ 0.05 and Fold change ≥ 1.5 folds) in the tumor samples, 5593 genes were up-regulated and 4864 were down-regulated. Some of the important pathways included VEGF signaling pathway (p=0.0019), TGF-beta signaling pathway (p=0.009), p53 signaling pathway (p=0.017), Insulin signaling pathway (p=0.032), Chemokine signaling pathway (p=0.011) and Wnt signaling pathway (p=0.05). Validation of the gene expression using real-time PCR showed significant up-regulation of HMGA2 and its downstream regulator LIN-28b, which is involved in self renewal pathway of fetal neural stem cells. In poorly differentiated tumors, ACVR1C expression was high, with low expression of SMAD2/3.
HMGA2, a neural stem cell self renewal signaling appears to be highly expressed in Retinoblastoma and could possibly be involved in the self renewal and differentiation of tumor cells.
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