NOV is a selective proapoptotic factor for human adrenocortical cells. Reduced expression of NOV in ACTs may play an important role in the process of childhood ACT tumorigenesis, accounting at least in part for the defect of apoptotic regression of the fetal adrenal that has been proposed to be responsible for tumor formation.

Nephroblastoma overexpressed gene (NOV) is highly expressed in the nervous system. We investigated its biological activity by expressing the human NOV gene (NOVH) in a human glioblastoma cell line that is negative for NOVH and by analyzing four clones with different levels of NOVH expression. There was no difference in cell proliferation between the NOVH-expressing cell lines, but there was increased cell adhesion and migration that correlated with increasing NOVH expression. Gene expression profiling was used to investigate the mechanisms by which NOVH expression regulated cell activity. We identified two induced genes in NOVH-expressing cells that are involved in cell migration: matrix metalloprotease (MMP)3 and platelet-derived growth factor receptor (PDGFR)-alpha. Our studies show that PDGFR-alpha induced MMP3 gene expression and increased cell proliferation and cell migration upon stimulation by platelet-derived growth factor (PDGF)-AA. We also show that the induction of MMP3 in cells expressing NOVH is potentiated by either cell density, serum, or PDGF-BB. Thus, expression of NOVH in glioblastoma cells triggers a cascade of gene expression resulting in increased cell adhesion and migration.