Shigemasa K, Tanimoto H, Underwood L J, Parmley T H, Arihiro K, Ohama K, O'Brien T J
Department of Obstetrics and Gynecology, Hiroshima University School of Medicine, Hiroshima 734-8551, Japan.
Int J Gynecol Cancer. 2001 Nov-Dec;11(6):454-61. doi: 10.1046/j.1525-1438.2001.01062.x.
We have previously reported that the stratum corneum chymotryptic enzyme (SCCE) is overexpressed in ovarian cancers and that SCCE has potential as a useful marker and/or a therapeutic target for ovarian carcinoma. Antileukoprotease (ALP) has been shown to be a specific inhibitor of SCCE. The objective of this study was to investigate the potential cotranscription and overexpression of ALP in carcinoma of the ovary. The expression of ALP transcript was evaluated by Northern blot hybridization and by semiquantitative polymerase chain reaction (PCR) technique. The presence of the ALP protein in ovarian tumor cells was evaluated by immunohistochemistry. Northern blot hybridization showed that the ALP transcript was abundant in ovarian carcinomas but was not detected in the normal ovary. Semi-quantitative PCR examination revealed that the mRNA level of ALP was significantly elevated in low-malignant-potential tumors and in ovarian carcinomas compared with that in normal ovaries (P < 0.01). There was significant positive correlation between SCCE and ALP mRNA overexpression status in ovarian tumor cases (P < 0.01). Immunohistochemical expression of ALP protein was observed in ovarian tumor cells, whereas little or no staining was observed in normal ovarian surface epithelium. Like SCCE, ALP is highly overexpressed in ovarian tumor cells, which begs the question of whether it remains an effective inhibitor of SCCE or whether it is discordant in time or space and is ineffective as an inhibitor of the SCCE enzyme.
我们之前曾报道过,角质层糜蛋白酶(SCCE)在卵巢癌中过表达,并且SCCE有潜力作为卵巢癌的有用标志物和/或治疗靶点。抗白细胞蛋白酶(ALP)已被证明是SCCE的特异性抑制剂。本研究的目的是调查ALP在卵巢癌中的潜在共转录和过表达情况。通过Northern印迹杂交和半定量聚合酶链反应(PCR)技术评估ALP转录本的表达。通过免疫组织化学评估卵巢肿瘤细胞中ALP蛋白的存在情况。Northern印迹杂交显示,ALP转录本在卵巢癌中丰富,但在正常卵巢中未检测到。半定量PCR检查显示,与正常卵巢相比,低恶性潜能肿瘤和卵巢癌中ALP的mRNA水平显著升高(P < 0.01)。在卵巢肿瘤病例中,SCCE和ALP mRNA过表达状态之间存在显著正相关(P < 0.01)。在卵巢肿瘤细胞中观察到ALP蛋白的免疫组织化学表达,而在正常卵巢表面上皮中观察到很少或没有染色。与SCCE一样,ALP在卵巢肿瘤细胞中高度过表达,这就引出了一个问题,即它是否仍然是SCCE的有效抑制剂,或者它在时间或空间上是否不一致,并且作为SCCE酶抑制剂无效。