We showed that PTEN expression was decreased significantly in trastuzumab-resistant NCI-N87/TR cells at both the gene and protein level, and that phosphorylation of AKT protein was up-regulated, indicating that PTEN down-regulation along with activation of the PI3K-AKT signaling pathways might be one of the major resistance mechanisms of gastric cancer to trastuzumab. The gene discussed is AKT1; the disease is gastric cancer.