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丝氨酸蛋白酶激肽释放酶7及其抑制剂抗白细胞蛋白酶在前列腺癌中的表达降低。

Expression of the serine protease kallikrein 7 and its inhibitor antileukoprotease is decreased in prostate cancer.

作者信息

Xuan Qiang, Yang Xiaoli, Mo Linjian, Huang Fengyu, Pang Youhong, Qin Min, Chen Zhiqiang, He Min, Wang Qi, Mo Zeng-Nan

机构信息

Institute of Urology, The First Affiliated Hospital of Guangxi Medical University, Nanning, China.

出版信息

Arch Pathol Lab Med. 2008 Nov;132(11):1796-801. doi: 10.5858/132.11.1796.

Abstract

CONTEXT

Kallikreins are a subgroup of serine proteases with diverse physiologic functions. It has been confirmed that kallikrein 7 (KLK7) is differentially expressed in ovarian and breast cancer. Antileukoprotease (ALP) has been shown to be a specific inhibitor of human kallikrein 7 (hK7). Antileukoprotease overexpression is commonly associated with aggressive, high-risk, or metastatic cancer originating from various organs.

OBJECTIVE

To investigate the expression and potential role of hK7 and its inhibitor ALP in prostate cancer.

DESIGN

The mRNA expression of KLK7 and ALP transcript in benign prostate epithelial cells and prostate cancers was evaluated by semiquantitative reverse transcription-polymerase chain reaction. We examined hK7 and ALP protein expression by immunohistochemistry in 20 normal prostate tissues, 50 benign prostatic hyperplasia tissues, and 103 prostate cancers. Western blot examination showed protein expression of hK7 and ALP in benign prostate epithelial cells and prostate cancer cell lines.

RESULTS

Semiquantitative polymerase chain reaction examination revealed that the mRNA level of KLK7 and ALP was significantly decreased in prostate cancers compared with that in benign prostate epithelial cells (P < .001). Immunohistochemical expression of hK7 was observed in prostate epithelial cells, whereas little or no staining was observed in prostate cancer. Western blot analysis revealed that hK7 and ALP were decreased in malignant prostate epithelium.

CONCLUSIONS

Like hK7, ALP is down-regulated in prostate cancers, which begs the question of whether it remains an effective inhibitor of hK7 or whether it is discordant in time or space and is ineffective as an inhibitor of hK7. The function of KLK7 and ALP in prostate cancer should be further studied.

摘要

背景

激肽释放酶是丝氨酸蛋白酶的一个亚群,具有多种生理功能。现已证实激肽释放酶7(KLK7)在卵巢癌和乳腺癌中存在差异表达。抗白细胞蛋白酶(ALP)已被证明是人类激肽释放酶7(hK7)的特异性抑制剂。抗白细胞蛋白酶的过表达通常与源自各种器官的侵袭性、高危或转移性癌症相关。

目的

研究hK7及其抑制剂ALP在前列腺癌中的表达及潜在作用。

设计

通过半定量逆转录-聚合酶链反应评估良性前列腺上皮细胞和前列腺癌中KLK7和ALP转录本的mRNA表达。我们采用免疫组织化学方法检测了20例正常前列腺组织、50例良性前列腺增生组织和103例前列腺癌中hK7和ALP蛋白的表达。蛋白质印迹检测显示了良性前列腺上皮细胞和前列腺癌细胞系中hK7和ALP的蛋白表达。

结果

半定量聚合酶链反应检测显示,与良性前列腺上皮细胞相比,前列腺癌中KLK7和ALP的mRNA水平显著降低(P <.001)。在前列腺上皮细胞中观察到hK7的免疫组织化学表达,而在前列腺癌中几乎没有或未观察到染色。蛋白质印迹分析显示恶性前列腺上皮中hK7和ALP减少。

结论

与hK7一样,ALP在前列腺癌中表达下调,这引发了一个问题,即它是否仍然是hK7的有效抑制剂,或者它在时间或空间上是否不一致且作为hK7的抑制剂无效。KLK7和ALP在前列腺癌中的功能应进一步研究。

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