Hu Kai, Gan Ye-Hua, Li Sheng-Lin, Gao Yan, Wu Deng-Cheng, Wang Cun-Yu, Yu Guang-Yan
Department of Oral and Maxillofacial Surgery, Peking University School and Hospital of Stomatology, Beijing 100081, PR China.
Oncol Rep. 2009 Jan;21(1):137-43.
Lung metastasis is one of the important characteristics of salivary adenoid cystic carcinoma (SACC). Although activation of extracellular signal-regulated kinase 1/2 (ERK1/2) pathway may be associated with cancer progression in some malignant tumors, its roles in lung metastasis of SACC remains unclear. We examined the expression of activated ERK1/2 in SACC-LM with high lung-metastatic rate and SACC-83 with low lung-metastatic rate, as well as in the tissues from lung-metastatic and non-metastatic groups of SACC patients. Western blot analysis indicated that SACC-LM exhibited higher expression of activated ERK1/2 than SACC-83. Similarly, immunohistochemistry showed that expression of activated ERK1/2 was detected in 73% (8/11) of the primary tissues from SACC patients with lung metastasis, while only 25% (3/12) of the primary tissues from SACC patients without lung metastasis (P<0.05). Furthermore, we examined the effects of U0126, a specific inhibitor of mitogen activated protein kinase kinase (MEK or MAPKK), on migration and invasion in SACC-LM cells, showing U0126 not only inactivated ERK1/2, but also inhibited migration and invasion of SACC-LM. The present findings suggested that the elevated expression of activated ERK1/2 may play a role in lung metastasis of salivary adenoid cystic carcinoma.
肺转移是涎腺腺样囊性癌（SACC）的重要特征之一。虽然细胞外信号调节激酶1/2（ERK1/2）通路的激活在某些恶性肿瘤中可能与癌症进展相关，但其在SACC肺转移中的作用仍不清楚。我们检测了肺转移率高的SACC-LM和肺转移率低的SACC-83中活化ERK1/2的表达，以及SACC患者肺转移组和非转移组组织中的表达。蛋白质印迹分析表明，SACC-LM中活化ERK1/2的表达高于SACC-83。同样，免疫组织化学显示，在有肺转移的SACC患者的73%（8/11）原发组织中检测到活化ERK1/2的表达，而在无肺转移的SACC患者的原发组织中仅25%（3/12）检测到（P<0.05）。此外，我们检测了丝裂原活化蛋白激酶激酶（MEK或MAPKK）的特异性抑制剂U0126对SACC-LM细胞迁移和侵袭的影响，结果显示U0126不仅使ERK1/2失活，还抑制了SACC-LM的迁移和侵袭。目前的研究结果表明，活化ERK1/2表达升高可能在涎腺腺样囊性癌的肺转移中起作用。
