Increased expression of h‐prune is associated with tumor progression and poor survival in gastric cancer

The human homolog of the Drosophila prune protein (from PRUNE, which encodes h‐prune), which interacts with glycogen synthase kinase 3, promotes cellular motility. H‐prune also interacts with nm23‐H1, a suppressor of cancer metastasis. It has been reported that stimulation of cellular motility by h‐prune is enhanced by its interaction with nm23‐H1 in breast cancer cells. In the present study, we examined the expression of h‐prune and nm23‐H1 during tumor progression in gastric cancer (GC). PRUNE mRNA was overexpressed in 12 (32%) of 38 GC cases by quantitative reverse transcription–polymerase chain reaction. PRUNE mRNA levels correlated significantly with advanced T grade, N grade and tumor stage. Immunohistochemical analysis revealed that 43 (30%) of 143 GC cases were positive for h‐prune, and h‐prune‐positive GC cases showed more advanced T grade, N grade and tumor stage than h‐prune‐negative GC cases. One hundred and twenty‐four (87%) of 143 GC cases were positive for nm23‐H1, and nm23‐H1 was expressed in almost all (42 cases, 98%) h‐prune‐positive GC cases. Many GC cases positive for both h‐prune and nm23‐H1 showed more advanced T grade, N grade and tumor stage than other type GC cases. Patients with h‐prune‐positive GC had a significantly worse survival rate than patients with h‐prune‐negative GC. These findings indicate that overexpression of h‐prune is associated with tumor progression and aggressiveness of GC. nm23‐H1 may enhance motility of cancer cells by interacting with h‐prune. (Cancer Sci 2007; 98: 1198–1205)