
<ArticleTitle>Change in gene expression subsequent to induction of <prot>Pnn</prot>/<prot>DRS</prot>/<prot>memA</prot>: increase in <prot>p21</prot>(<prot>cip1</prot>/<prot>waf1</prot>).</ArticleTitle>
<AbstractText><prot>Pnn</prot> (<prot>PNN</prot>) is a nuclear and cell adhesion-related protein. Previous work has suggested that <prot>Pnn</prot>/<prot>DRS</prot>/<prot>memA</prot> is a potential tumor suppressor involved in the regulation of cell adhesion and cell migration. Using the ecdysone-inducible mammalian expression system, a stable inducible <prot>GFP</prot>-tagged human <prot>Pnn</prot> gene (<prot>PNNGFP</prot>) expressing 293 cell line was created (EcR293-<prot>PNNGFP</prot>). Cells induced to express <prot>PNNGFP</prot> not only exhibited increased cell-cell adhesion but also exhibited changes in cell growth and cell cycle progression. cDNA array analyses, together with real time PCR, revealed that the effects of exogenously expressed <prot>Pnn</prot> on cellular behavior may be linked to the regulation of the expression of specific subset genes. This subset includes cell cycle-related genes such as <prot>p21</prot>(<prot>cip1</prot>/<prot>waf1</prot>), <prot>CDK4</prot>, <prot>CPR2</prot>; cell migration and invasion regulatory genes such as <prot>RhoA</prot>, <prot>CDK5</prot>, <prot>TIMP-1</prot>, <prot>MMP-7</prot>, and <prot>EMMPRIN</prot>; and <prot>MIC-1</prot>. Concordant with previous observations of <prot>Pnn</prot>-induced phenotype changes, genes coding for epithelial associated processes and cell division controls were elevated, while those coding for increased cell motility and cellular reorganizations were downregulated. We utilized <prot>p21</prot> promoter-luciferase reporter constructs and demonstrated that a marked stimulation of <prot>p21</prot> promoter activity in 293 cells correlated with increased <prot>Pnn</prot> expression. Taken together, these data indicate that <prot>Pnn</prot> may participate in the regulation of gene expression, thereby, positively promoting cell-cell adhesion, and negatively affecting cell migration and cell proliferation.</AbstractText>
