P38MAPK信号通路与uPA在卵巢癌细胞及组织中表达的相关性

doi:10.3969/j.issn.1007-3969.2015.08.003

中国癌症杂志 ›› 2015, Vol. 25 ›› Issue (8): 572-578.doi: 10.3969/j.issn.1007-3969.2015.08.003

P38MAPK信号通路与uPA在卵巢癌细胞及组织中表达的相关性

邹存华¹，王　宏²，宋冬冬³，南　平¹，盛　梅¹

1. 胜利油田中心医院妇产科，山东东营257000 ；
2. 胜利油田中心医院保健科，山东东营257000 ；
3. 胜利油田中心医院胃肠外科，山东东营257000

出版日期:2015-08-30 发布日期:2015-12-14
通信作者: 盛梅　E-mail：shengmei1967@163.com
基金资助:
国家自然科学基金资助项目(30970651)；国家重点实验室基金资助项目(SKLZZ200907)。

Correlation between P38 mitogen-activated protein kinase signal transduction pathway and uPA expression in ovarian cancer

ZOU Cunhua¹, WANG Hong², SONG Dongdong³, NAN Ping¹, SHENG Mei¹

1.Department of Gynecology and Obstetrics, Shengli Oilfield Central Hospital, Dongying Shandong 257000, China; 2.Department of Health Division, Shengli Oilfield Central Hospital, Dongying Shandong 257000, China; 3.Department of Gastrointestinal Surgery, Shengli Oilfield Central Hospital, Dongying Shandong 257000, China

Published:2015-08-30 Online:2015-12-14
Contact: SHENG Mei E-mail: shengmei1967@163.com

摘要/Abstract

摘要： 背景与目的：P38丝裂原活化蛋白激酶(P38 mitogen-activated protein kinase，P38MAPK)信号通路参与多种肿瘤的发生、发展和转移过程，尿激酶型纤溶酶原激活剂(urokinase-type plasminogen activator，uPA)在肿瘤浸润和转移中发挥着重要作用。本实验研究卵巢癌组织中P38MAPK、细胞外信号调节激酶(extracellular signal-regulated kinase，ERK)、丝氨酸苏氨酸蛋白激酶(serine threonine kinase，AKT)及uPA的表达与临床病理特征的关系，并分析上述蛋白与uPA表达的相关性，探讨P38MAPK信号通路与uPA在卵巢癌细胞及组织中的表达及临床意义。方法：应用免疫组织化学法检测49例卵巢癌组织中uPA、P38MAPK、ERK和AKT蛋白的表达，采用蛋白［质］印迹法(Western blot)检测不同卵巢癌细胞系HO8910、HO-8910PM、SKOV3和CAOV3中uPA和P38MAPK蛋白的表达，使用特异性抑制剂SB203580阻断P38MAPK信号通路后检测uPA蛋白表达水平的变化。结果：uPA、P38MAPK、ERK和AKT蛋白在卵巢癌组织中的表达阳性率分别为61.22%、57.14%、53.06%和55.10%。uPA蛋白的表达与P38MAPK呈正相关(r=0.865，P=0.001)，且与卵巢癌组织的临床病理分期(P=0.029)、分化(P=0.03)和转移程度(P_淋巴=0.022，P_大网膜=0.012)有关，而与患者的年龄(P=0.754)及组织学类型(P=0.652)无关。ERK、AKT蛋白的表达与卵巢癌淋巴结转移(P_ERK=0.011，P_AKT=0.022)和大网膜转移(P_ERK=0.006，P_AKT=0.000)有关，而与患者的年龄(P_ERK=0.000，P_AKT=0.022)、组织类型(P_ERK=0.771，P_AKT=0.245)及病理分期(P_ERK=1.000，P_AKT=0.254)无关。卵巢癌细胞系HO-8910PM中uPA蛋白的表达水平明显高于HO8910、SKOV3和CAOV3细胞系，使用SB203580阻断P38MAPK信号通路后可降低uPA蛋白的表达，且随着SB203580浓度升高uPA蛋白表达水平逐渐降低。卵巢癌中P38MAPK及uPA蛋白的表达与卵巢癌的预后显著相关(Log-rank=3.897和11.044，P=0.048和0.001)。结论：卵巢癌组织中P38MAPK信号通路处于激活状态；P38MAPK信号通路的激活可上调uPA的表达，促进卵巢癌的恶性进展；P38MAPK信号通路和uPA可能在卵巢癌侵袭和转移的过程中发挥重要作用。P38MAPK和uPA蛋白有望成为卵巢癌预后评估的重要指标。

关键词: 卵巢癌, 尿激酶型纤溶酶原激活剂, 细胞外信号调节激酶, 丝氨酸/苏氨酸蛋白激酶, P38丝裂原活化蛋白激酶信号通路

Abstract: Background and purpose: P38 mitogen-activated protein kinase (P38MAPK) signal transduction pathway is involved in occurrence, development and transfer process in a wide variety of tumors. Urokinase-type plasminogen activator (uPA) plays an important role in tumor invasion and metastasis. This study aimed to explore the clinical significance of the P38MAPK signaling pathway and the expression of uPA in ovarian cancer. Methods: The expressions of uPA, P38MAPK, ERK and AKT were detected in 49 cases of cervical adenocarcinoma by immunohistochemistry. The expressions of uPA and P38MAPK were detected by Western blot in ovarian cancer cell lines HO8910, HO-8910PM, SKOV3 and CAOV3. The changes of uPA and P38MAPK were detected by SB203580, a specific inhibitor of P38MAPK signal transduction pathway. Results: The result of immunohistochemical method showed that positive expression rates for uPA, P38MAPK, ERK and AKT were 61.22%, 57.14%, 53.06% and 55.10%, respectively. The expression of the uPA was positively correlated with the P38MAPK (r=0.865, P=0.001), and related with clinicopathologic stage, differentiated degree, lymph node metastasis, but not related with age and histologic type (P>0.05). The expressions of AKT and ERK were related with the lymph node metastasis and greater omentum metastasis (P<0.05), but not related with age and histologic type (P>0.05). The expression of uPA in HO-8910PM was higher than that in ovarian cancer cell lines HO8910, SKOV3 and CAOV3, and the expression of uPA reduced when the P38MAPK signal transduction pathway was cut off by the SB203580. The expressions of P38MAPK and uPA were negatively correlated with the prognosis of ovarian cancer (Log-rank=3.897 and 11.044, P=0.048 and 0.001). Conclusion: The P38MAPK signal transduction pathway was activated in ovarian cancer. The activated P38MAPK signal transduction pathway can raise the expression of uPA, which may contribute to the development of ovarian cancer. The result indicates that the P38MAPK signal transduction pathway and uPA might play an important role in the invasion and metastasis of ovarian cancer. P38MAPK and uPA might be useful markers for evaluating prognosis of ovarian cancer.

Key words: Ovarian cancer, Urokinase-type plasminogen activator, Extracellular signal-regulated kinase, Serine threonine kinase, P38 mitogen-activated protein kinase signal transduction pathway

邹存华,王　宏,宋冬冬,等. P38MAPK信号通路与uPA在卵巢癌细胞及组织中表达的相关性[J]. 中国癌症杂志, 2015, 25(8): 572-578.

ZOU Cunhua, WANG Hong, SONG Dongdong, et al. Correlation between P38 mitogen-activated protein kinase signal transduction pathway and uPA expression in ovarian cancer[J]. China Oncology, 2015, 25(8): 572-578.

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P38MAPK信号通路与uPA在卵巢癌细胞及组织中表达的相关性

Correlation between P38 mitogen-activated protein kinase signal transduction pathway and uPA expression in ovarian cancer

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