Similar to the inverse correlation between EZH2 and CT/TET2 expression we Dextrose report here, others have shown EZH2 and TET enzymes to repress and induce differentiation of neuronal precursors, respectively. CT genes are up-regulated during the initial stages of development in the human embryo, but decrease as tissues differentiate further. As adult colon tissue does not show PAGE2 or SPANX-B expression, had Caco-2 cells the capability of differentiating further, both genes might have been down-regulated completely. On the other hand, the fact that we could not demonstrate up-regulation of GAGE, MAGE-A3, NY-ESO-1 or SSX4 expression in this model might be because these genes are expressed at earlier stages of differentiation. We believe this because SPANX-B expression is primarily in post-meiotic cells of the testis, whereas GAGE, MAGE-A3, NY-ESO-1 or SSX expression is primarily in spermatogonia. Our data and that of several others�� indicate that cancer cells that express CT genes have more of an epithelial rather than a mesenchymal phenotype. We suggest that CT genes PAGE2 and SPANX-B are induced during a window of differentiation that correlates with up-regulation of epithelial markers of differentiation. The Caco-2 SD model has made it possible to observe the actively changing epigenetic landscape within the promoters of these CT genes. However, as CT gene expression in tumors has closely been related to the methylation state of their promoter, the process that leads to CT gene induction in vivo might ultimately result in ����fixing���� of the epigenetic state which would in turn result in CpG methylation. Yet, via dynamic MET in tumors, it is conceivable that even this might Cephalothin sodium change over the course of the disease. From a clinical perspective, data from our lab as well as from others reveal that sub-grouping of tumors based on gene expression profiles can clearly identify cells with different chemosensitivity profiles. In this line, we predict future studies will reveal distinct drug sensitivity profiles for colorectal cancer subtypes as possibly defined by PAGE2 and SPANX-B expression, for which the Caco-2 SD model could be used.