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胃癌中激肽释放酶相关肽酶6(KLK6)的上调与分泌

Upregulation and secretion of kallikrein-related peptidase 6 (KLK6) in gastric cancer.

作者信息

Kim Jin Ju, Kim Jong-Tae, Yoon Hyo Ran, Kang Min Ah, Kim Joo Heon, Lee Young-Ha, Kim Jae Wha, Lee Seon-Jin, Song Eun Young, Myung Pyung Keun, Lee Hee Gu

机构信息

Medical Genomics Research Center, Korea Research Institute of Bioscience and Biotechnology, 125 Gwahak-ro, Yuseong-gu, Daejeon 305-806, Republic of Korea.

出版信息

Tumour Biol. 2012 Jun;33(3):731-8. doi: 10.1007/s13277-011-0267-1. Epub 2012 Feb 29.

Abstract

KLK6 encoding kallikrein-related peptidase 6, a trypsin-like serine protease, has been shown to be upregulated in several cancers, although the tumorigenic role of KLK6 has not been elucidated. In this study, KLK6 was identified as a highly upregulated gene in gastric cancer; therefore, the possibility that KLK6 might be a suitable candidate tumor marker was examined. RT-PCR and immunohistochemical analysis showed overexpression of KLK6 in gastric cancer tissues compared to nontumor regions. Sera from gastric cancer patients had a 1.7-fold increase in KLK6 (373.1 μg/L, P = 0.048) compared to healthy individuals (214.2 μg/L), although there was no significant difference among patients with various tumor stages. Cellular invasiveness decreased by 45% in cells transfected with KLK6-specific small interfering RNA. Exogenous overexpression of KLK6 led to decreased activity of the E-cadherin promoter. This study shows that KLK6 is significantly upregulated and secreted in gastric cancer tissues and sera, suggesting that KLK6 might be used as a potential biomarker and therapeutic target for gastric cancer.

摘要

KLK6编码激肽释放酶相关肽酶6,一种类胰蛋白酶丝氨酸蛋白酶,已被证明在多种癌症中上调,尽管KLK6的致瘤作用尚未阐明。在本研究中,KLK6被鉴定为胃癌中高度上调的基因;因此,研究了KLK6可能是合适的候选肿瘤标志物的可能性。逆转录聚合酶链反应(RT-PCR)和免疫组织化学分析显示,与非肿瘤区域相比,KLK6在胃癌组织中过表达。与健康个体(214.2μg/L)相比,胃癌患者血清中KLK6增加了1.7倍(373.1μg/L,P = 0.048),尽管不同肿瘤分期的患者之间没有显著差异。用KLK6特异性小干扰RNA转染的细胞中细胞侵袭性降低了45%。KLK6的外源性过表达导致E-钙黏蛋白启动子活性降低。本研究表明,KLK6在胃癌组织和血清中显著上调并分泌,提示KLK6可能作为胃癌的潜在生物标志物和治疗靶点。

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