首都医科大学学报 ›› 2019, Vol. 40 ›› Issue (1): 59-64.doi: 10.3969/j.issn.1006-7795.2019.01.011

• 泌尿系统肿瘤:基础研究与临床实践 • 上一篇    下一篇

单羧酸转运蛋白4(MCT4)在前列腺癌中的表达及调控研究

平浩1, 马林祥2, 王明帅2, 龙军3, 牛亦农2, 刘跃新1, 邢念增4   

  1. 1. 首都医科大学附属北京同仁医院泌尿外科, 北京 100730;
    2. 首都医科大学附属北京朝阳医院泌尿外科, 北京 100020;
    3. 首都医科大学基础医学院免疫学系, 北京 100069;
    4. 国家癌症中心 国家肿瘤临床医学研究中心 中国医学科学院北京协和医学院肿瘤医院, 北京 100021
  • 收稿日期:2018-10-24 出版日期:2019-01-21 发布日期:2019-01-23
  • 通讯作者: 平浩 E-mail:pinghaocy@163.com
  • 基金资助:
    国家自然科学基金(面上项目)(81772698),首都医科大学基础临床科研合作基金(16JL60)。

Expression and regulation of monocarboxylate transporters 4(MCT4) in prostate cancer

Ping Hao1, Ma Linxiang2, Wang Mingshuai2, Long Jun3, Niu Yinong2, Liu Yuexin1, Xing Nianzeng4   

  1. 1. Department of Urology, Beijing Tongren Hospital, Capital Medical University, Beijing 100730, China;
    2. Department of Urology, Beijing Chaoyang Hospital, Capital Medical University, Beijing 100020, China;
    3. Department of Immunology, School of Basic Medical Sciences, Capital Medical University, Beijing 100069, China;
    4. National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
  • Received:2018-10-24 Online:2019-01-21 Published:2019-01-23
  • Supported by:
    This study was supported by National Natural Science Foundation of China(81772698), Basic-Clinical Cooperation Program from Capital Medical University(16JL60).

摘要: 目的 探讨单羧酸转运蛋白4(monocarboxylate transporters 4,MCT4)在前列腺癌组织及细胞系中的表达情况,明确其在前列腺癌细胞中的调控作用。方法 应用免疫组织化学方法检测MCT4蛋白在前列腺癌(prostate cancer,PCa)、良性前列腺增生(benign prostatic hyperplasia,BPH)及癌旁组织(para-carcinoma tissues,PCT)中的表达,分析其与前列腺癌Gleason评分及淋巴结转移的关系。免疫印迹(Western blotting)法检测不同前列腺癌细胞系中MCT4蛋白表达差异,分析抑制MCT4蛋白表达对N-cadherin、E-cadherin及pERK1/2的调控作用。结果 免疫组化检测显示,MCT4蛋白在前列腺癌、前列腺增生及癌旁组织中均有表达;但PCa中MCT4表达水平明显高于BPH及PCT(P=0.003)。另外,MCT4蛋白表达与前列腺癌是否有淋巴结转移密切相关,转移组显著高于非转移组(P=0.022)。Western blotting检测结果显示,在前列腺正常上皮细胞及激素依赖性前列腺癌细胞LNCap中MCT4表达较弱,而在恶性程度较高的去势抵抗性前列腺癌细胞PC3及DU145中表达明显增强。抑制PC3细胞中MCT4表达可以使N-cadherin及pERK1/2的蛋白表达下降,而使E-cadherin蛋白表达水平升高。结论 单羧酸转运蛋白4可能参与上皮间质转化(epithelial-mesenchymal transition,EMT)进程及ERK1/2通路的调控,促进前列腺癌的进展和转移,对前列腺癌的临床诊断和治疗有重要意义。

关键词: 前列腺癌, 单羧酸转运蛋白4, 淋巴结转移, 调控作用

Abstract: Objective To investigate the expression and clinical significance of monocarboxylate transporters 4(MCT4) in prostate cancer(PCa), and explore the regulation mechanism of MCT4 in PCa. Methods The expression of MCT4 was detected by immunohistochemistry in PCa, benign prostatic hyperplasia(BPH) and para-carcinoma tissues(PCT). The relation between the expression and clinicopathological changes was analyzed statistically. The expression of MCT4 was examined with Western blotting in prostate cancer cells. The effects on N-cadherin, E-cadherin and pERK1/2 by inhibition of MCT4 was also analyzed. Results The expression of MCT4 in PCa was significantly higher than those in BPH and PCT (P=0.003). Furthermore, the increased expression of MCT4 protein was significantly associated with the presence of lymph node metastasis of PCa(P=0.022). The Western blotting indicated that, the expression of MCT4 protein was higher in PC3 and DU145 than in RWPE-1 and LNCap cell lines. With inhibition of MCT4, the level of N-cadherin and pERK1/2 was decreased, while that of E-cadherin was increased. Conclusion The expression of MCT4 may be involved in the regulation of epithelial-mesenchymal transition (EMT) and ERK1/2, and it is closely related to the metastasis of PCa. The expression of MCT4 has significant clinical implications for diagnosis and treatment of PCa.

Key words: prostate cancer, monocarboxylate transporters 4, lymph node metastasis, regulation

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