Department of Gastroenterology, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University, Shanghai, China.
Int J Immunopathol Pharmacol. 2012 Jul-Sep;25(3):583-90. doi: 10.1177/039463201202500304.
Yes-associated protein (YAP) has been implicated as an oncogene in multiple human cancers. In the present study, human gastric adenocarcinoma tissues of different grades (N=78) were collected and the mRNA and protein expression of YAP and phosphorylated YAP (p-YAP) in gastric adenocarcinomas were evaluated using immunohistochemistry, Real-time PCR and Western blot assays. Then, human gastric cancer SGC-7901 cells were stably transfected with lentivirus-mediated YAP small hairpin RNA (shRNA). The expression levels of YAP, proliferating cell nuclear antigen (PCNA) and metalloproteinase-2 (MMP-2) were detected and the effects of shRNA-mediated knockdown of YAP on cell proliferation and metastasis were assessed in gastric cancer cells. As a result, the expression of YAP was observed in 69.23 percent gastric adenocarcinoma tissues, elevating with the ascending order of tumor malignancy. Knockdown of YAP could down-regulated the expression of PCNA and MMP-2, and inhibit the proliferation and metastasis of gastric cancer cells. In conclusion, YAP is strongly expressed in gastric adenocarcinomas, and knockdown of YAP may inhibit gastric cancer cell proliferation and metastasis through down-regulation of PCNA and MMP-2 expression, suggesting that YAP represents an important therapeutic target in human gastric cancer.
Yes 相关蛋白（YAP）已被认为是多种人类癌症的致癌基因。在本研究中，收集了不同分级的人胃腺癌组织（N=78），并通过免疫组织化学、实时 PCR 和 Western blot 检测评估胃腺癌中 YAP 和磷酸化 YAP（p-YAP）的 mRNA 和蛋白表达。然后，通过慢病毒介导的 YAP 短发夹 RNA（shRNA）稳定转染人胃癌 SGC-7901 细胞。检测 YAP、增殖细胞核抗原（PCNA）和基质金属蛋白酶-2（MMP-2）的表达水平，并评估 shRNA 介导的 YAP 敲低对胃癌细胞增殖和转移的影响。结果，在 69.23%的胃腺癌组织中观察到 YAP 的表达，随着肿瘤恶性程度的升高而升高。YAP 的敲低可下调 PCNA 和 MMP-2 的表达，并抑制胃癌细胞的增殖和转移。总之，YAP 在胃腺癌中强烈表达，通过下调 PCNA 和 MMP-2 的表达，YAP 的敲低可能抑制胃癌细胞的增殖和转移，提示 YAP 是人类胃癌的一个重要治疗靶点。
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