Transcriptome Analysis Suggests PKD3 Regulates Proliferative Glucose Metabolism, Calcium Homeostasis and Microtubule Dynamics After MEF Spontaneous Immortalization.

Cell immortalization corresponds to a biologically relevant clinical feature that allows cells to acquire a high proliferative potential during carcinogenesis. In multiple cancer types, Protein Kinase D3 (PKD3) has often been reported as a dysregulated oncogenic kinase that promotes cell proliferation. Using mouse embryonic fibroblasts (MEFs), in a spontaneous immortalization model, PKD3 has been demonstrated as a critical regulator of cell proliferation after immortalization. However, the mechanisms by which PKD3 regulates proliferation in immortalized MEFs require further elucidation. Using a previously validated -deficient MEF model, we performed a poly-A transcriptomic analysis to identify putative -regulated biological processes and downstream targets in MEFs after spontaneous immortalization. To this end, differentially expressed genes (DEGs) were identified and further analyzed by gene ontology (GO) enrichment and protein-protein interaction (PPI) network analyses to identify potential hub genes. Our results suggest that modulates proliferation through the regulation of gene expression associated with glucose metabolism (, , , ), calcium homeostasis and transport ( and ) and microtubule dynamics ( and ). These candidate processes and associated genes represent potential mechanisms involved in -induced proliferation in spontaneously immortalized cells as well as clinical targets in several cancer types.