Department of Pathology, Cancer Research Institute, Chungnam National University, School of Medicine, Daejeon, South Korea.
Pathol Res Pract. 2011 Jul 15;207(7):428-32. doi: 10.1016/j.prp.2011.05.004. Epub 2011 Jun 15.
Dual specificity phosphatase 6 (DUSP6) is a member of the MAP kinase phophatase family. DUSP6 inactivates extracellular signal-regulated kinase (ERK), belonging to the MAP kinase family, and can act in tumor suppressive pathways. The aim of this study was to investigate associations of DUSP6 expression with expression of ERK and Ki-67 and with clinicopathological parameters in lung adenocarcinoma and squamous cell carcinoma. A total of 102 squamous cell carcinomas and 66 adenocarcinomas were studied using immunohistochemistry for DUSP6, ERK1/2, and Ki-67. In 66 adenocarcinomas, high DUSP6 expression was positively correlated with ERK1/2 expression. High DUSP6 expression was correlated with lower histological grade and lower Ki-67 index in the adenocarcinomas. In 102 squamous cell carcinomas, high DUSP6 expression was correlated with lower ERK expression, with greater smoking pack-years, but not with the Ki-67 index. These results indicate that DUSP6 acts as a negative feedback regulator of ERK in adenocarcinoma progression, but that DUSP6 does not play a role in the downregulation of ERK in squamous cell carcinoma. The differential expression of DUSP6 correlated with Ki-67 index, suggesting that DUSP6 plays an important role in cancer resistance in different subtypes of non-small cell lung carcinoma.
双重特异性磷酸酶 6(DUSP6)是丝裂原激活蛋白激酶磷酸酶家族的成员。DUSP6 使细胞外信号调节激酶(ERK)失活,ERK 属于丝裂原激活蛋白激酶家族,可作用于肿瘤抑制途径。本研究旨在探讨 DUSP6 表达与 ERK 和 Ki-67 表达以及肺腺癌和鳞癌临床病理参数之间的关系。采用免疫组织化学法检测 102 例鳞癌和 66 例腺癌中 DUSP6、ERK1/2 和 Ki-67 的表达。在 66 例腺癌中,高 DUSP6 表达与 ERK1/2 表达呈正相关。在腺癌中,高 DUSP6 表达与组织学分级较低和 Ki-67 指数较低相关。在 102 例鳞癌中,高 DUSP6 表达与 ERK 表达降低、吸烟包年数增加相关,但与 Ki-67 指数无关。这些结果表明,DUSP6 在腺癌进展中作为 ERK 的负反馈调节剂发挥作用,但在鳞癌中 DUSP6 不参与 ERK 的下调。DUSP6 的表达与 Ki-67 指数相关,表明 DUSP6 在不同类型的非小细胞肺癌的癌症耐药中发挥重要作用。