Transcriptional Dynamics of Immortalized XXXX Mesenchymal Stem Cells during Transformation.

@entity1 @entity242 @entity5 @entity7433 @entity19 @entity1799 @entity74 @entity1344 @entity2750 @entity2215 @entity27362
UNASSIGNED: Comprehensive analysis of alterations in gene expression along with neoplastic transformation in @entity1 cells provides valuable information about the molecular mechanisms underlying transformation. To further address these questions, we performed whole transcriptome analysis to the @entity1 mesenchymal stem cell line, UE6E7T-3, which was immortalized with @entity2215 and @entity1799 E6/E7 genes, in association with progress of transformation in these cells. At early stages of culture, UE6E7T-3 cells preferentially lost one copy of chromosome 13, as previously described; in addition, @entity5 suppressor genes, DNA repair genes, and apoptosis-activating genes were overexpressed. After the loss of chromosome 13, additional @entity74 that drove progressive transformation, were observed. At this stage, the cell line expressed oncogenes as well as genes related to anti-apoptotic functions, cell-cycle progression, and @entity1344 ( @entity1344 ); these pro-tumorigenic changes were concomitant with a decrease in @entity5 suppressor gene expression. At later stages after prolong culture, the cells exhibited chromosome translocations, acquired anchorage-independent growth and @entity7433 in @entity19 , ( @entity242 ) and exhibited increased expression of genes encoding growth factor and DNA repair genes, and decreased expression of adhesion genes. In particular, @entity27362 ( @entity27362 ), which encodes a cell-surface proteoglycan that might be a biomarker for @entity242 , was expressed at high levels in association with transformation. Patched ( @entity2750 ), the cell surface receptor for hedgehog (Hh) signaling, was also significantly overexpressed and co-localized with @entity27362 . Knockdown of @entity27362 expression decreased cell proliferation, suggesting that it plays a key role in growth in U3-DT cells (transformants derived from UE6E7T-3 cells) through the Hh signaling pathway. Thus, the UE6E7T-3 cell culture model is a useful tool for assessing the functional contribution of genes showed by expression profiling to the neoplastic transformation of @entity1 fibroblasts and @entity1 mesenchymal stem cells (hMSC).
