is negatively regulated by Kit in gastrointestinal stromal tumors.

Our group has previously demonstrated that pfetin, encoded by the gene, is a strong prognostic biomarker for gastrointestinal stromal tumors (GISTs). However, the underlying mechanisms that control pfetin expression remain unknown. To elucidate the regulatory mechanisms of in GIST, in addition to a possible association between alterations and protein expression, we examined 76 patients with GISTs for mutations by PCR-direct sequence, and compared these results with clinicopathologic data. The function of pfetin in GIST progression was also revealed using GIST T1 cells. In this series, pfetin expression was not observed in 15 cases, and loss of pfetin expression was associated with higher mitotic rate (>5/50HPFs: = 0.029). There was also a trend between presence of necrosis and loss of pfetin expression but this was not statistically significant ( = 0.09). mutations were frequently observed in 22 out of 76 GISTs (28.9%); however, they did not affect protein expression and were not associated with patients' prognosis. knockdown resulted in the accelerated growth of GIST T1 cells, confirming that pfetin functions as a tumor suppressor. knockdown significantly inhibited cellular growth and upregulated the expression of pfetin at both the mRNA and protein level. These findings suggest that GISTs with loss of pfetin expression has proliferative advantage and that higher pfetin expression in GISTs may be indicative of lower expression levels of . This relationship confirms that pfetin is a useful prognostic marker in GISTs.