Cell adhesion pathways in mouse retinoblastoma

B66 It is well established that the initiating genetic lesion for retinoblastoma is inactivation of the RB1 gene presumably in proliferating retinal progenitor cells in utero. Recent studies have indicated that the second genetic lesion is suppression of the p53 pathway by MDMX amplification. We have generated a mouse model of retinoblastoma from Rb+/-;p107-/-;p53-/- retinal progenitor cells. Clonal lines were derived from this tumor that was of 2 distinct morphologies - one that grew as aggregates in suspension and the other that grew attatched to the substrate. To further characterize changes in the retinoblastoma cells, microarray analysis of each of the clones and primary tumors were performed. Some of the genes that showed 2-fold changes were Alpha-Catenin, Cdh11, Egf, Egfr, Itga4, Itgav, Itgb6, MMP9, PDGFD, RhoB, Stat5a and Stat5b and we are in the process of confirming these expression levels by Real-Time PCR. Immunostaining and western blotting also show differences in levels and localization of some of these genes among the adherent and non-adherent clones. We predict that these differences could be associated with differences in morphologies and adhesiveness among the adherent and non-adherent clones.