Up-Regulation and Clinical Significance of Serine Protease Kallikrein 6 in Colon Cancer
Up-Regulation and Clinical Significance of Serine Protease Kallikrein 6 in Colon Cancer
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DOI：
10.1002/cncr.25841
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发表时间：
2011-06-15
期刊：
影响因子：
6.2
通讯作者：
Lee, Hee Gu
中科院分区：
文献类型：
--
作者：
Kim, Jong-Tae;Song, Eun Young;Lee, Hee Gu
背景技术背景：激肽释放酶相关肽酶6（KLK 6）编码在几种癌症中上调的胰蛋白酶样丝氨酸蛋白酶，尽管KLK 6在癌症中的推定功能尚未阐明。在当前的研究中，在结肠癌中鉴定了KLK 6的过表达，并检查了KLK 6可能是作为肿瘤标志物的合适候选物的可能性。方法：采用逆转录-聚合酶链反应、免疫组化和临床病理分析检测结肠癌组织中KLK 6的信使RNA（mRNA）转录水平和蛋白上调。细胞增殖，侵袭性，和抗凋亡活性在结肠癌细胞中，用小干扰RNA（siRNA）转染的KLK 6。结果：肿瘤组织中KLK 6 mRNA表达明显高于非肿瘤组织。KLK 6蛋白在腺癌中强表达，但在正常粘膜或癌前发育不良病变中不表达。结肠癌患者的血清显示，与非癌细胞（0.19 μ g/mL）相比，KLK 6分泌增加（0.25 μ g/mL; P= 0.031）。对143例结肠癌患者的临床病理和免疫组化研究显示，KLK 6表达与Dukes病分期之间存在显著相关性（P=.005）。KLK 6高表达与较短的总生存期（P=.001）和无复发生存期（P=.001）显著相关。在转染KLK 6 siRNA的细胞中，增殖和侵袭率降低了50%。KLK 6的过表达导致E-钙粘蛋白启动子活性降低。结论：KLK 6在结肠癌患者的组织和血清中显著上调，并且与不良预后密切相关，表明KLK 6可能用作结肠癌的潜在生物标志物和治疗靶点。Cancer 2011; 117：2608-19. (C)2010美国癌症协会
BACKGROUND: Kallikrein-related peptidase 6 (KLK6) encodes a trypsin-like serine protease that is up-regulated in several cancers, although the putative functions of KLK6 in cancer have not been elucidated. In the current study, overexpression of KLK6 was identified in colon cancer, and the possibility that KLK6 may be a suitable candidate as a tumor marker was examined. METHODS: Messenger RNA (mRNA) transcript levels and protein up-regulation of KLK6 in colon cancer tissues was examined using reverse transcriptase-polymerase chain reaction, immunohistochemistry, and clinicopathologic analyses. Cell proliferation, invasiveness, and antiapoptotic activity were determined in colon cancer cells that were transfected with small-interfering RNA (siRNA) of KLK6. RESULTS: KLK6 mRNA was up-regulated significantly in tumor tissues compared with nontumor regions. KLK6 protein was strongly expressed in adenocarcinomas but was not expressed in normal mucosa or in premalignant dysplastic lesions. Sera from patients with colon cancer revealed an increase in KLK6 secretion (0.25 mu g/mL; P=.031) compared with noncancer cells (0.19 mu g/mL). Clinicopathologic and immunohistochemical studies of 143 patients with colon cancer revealed a significant correlation between KLK6 expression and Dukes disease stage (P=.005). High KLK6 expression was associated significantly with shorter overall (P=.001) and recurrence-free survival (P=.001). The rates of proliferation and invasiveness were decreased by 50% in cells that were transfected with KLK6 siRNA. The overexpression of KLK6 led to decreased activity of the E-cadherin promoter. CONCLUSIONS: KLK6 was up-regulated significantly in tissues and sera from patients with colon cancer and was associated closely with a poor prognosis, suggesting that KLK6 may be used as a potential biomarker and a therapeutic target for colon cancer. Cancer 2011; 117: 2608-19. (C) 2010 American Cancer Society.