Serine proteases HTRA1 and HTRA3 are down-regulated with increasing grades of human endometrial cancer
Serine proteases HTRA1 and HTRA3 are down-regulated with increasing grades of human endometrial cancer
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DOI：
10.1016/j.ygyno.2006.03.006
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发表时间：
2006-10-01
影响因子：
4.7
通讯作者：
Nie, Guiying
中科院分区：
文献类型：
--
作者：
Bowden, Marissa A.;Di Nezza-Cossens, Lisa A.;Nie, Guiying
目标。高温需要量因子A （HTRA）家族由丝氨酸蛋白酶组成，其结构域与细菌HTRA结构域同源。已经描述了四名人类HTRA成员：HTRA1-4。HTRA1和HTRA3具有高度的结构域同源性，因此可能具有功能相似性。据报道，在sv40转化的细胞、恶性黑色素瘤细胞系、卵巢肿瘤和卵巢癌细胞系中，HTRA1 mRNA和蛋白下调，表明HTRA1和蛋白在癌症中逐渐丧失。这就提出了HTRA3可能同样与癌症有关的可能性。本研究检测了HTRA1和HTRA3在人子宫内膜癌组织中的mRNA和蛋白表达水平。逆转录聚合酶链反应（RT-PCR）在正常子宫内膜（n = 4）和三个EC级别（每个EC级别n = 5）中进行分析。采用免疫组化方法检测HTRA1和HTRA3在正常子宫内膜组织（n = 6）和三个EC级别（n = 8-10）中的蛋白表达和细胞定位。RT-PCR分析显示，与正常子宫内膜相比，子宫内膜癌中HTRA1和HTRA3 mRNA显著降低。HTRA1和HTRA3蛋白在EC组织中的表达模式相似。免疫染色阳性，半定量评分，显示HTRA1和3蛋白表达随着ec分级的增加而显著降低。这些数据表明HTRA1和HTRA3 mRNA和蛋白水平随着EC分级的增加而降低。(c) 2006爱思唯尔公司版权所有。
Objective. The high temperature requirement factor A (HTRA) family consists of serine proteases with domains homologous to those of bacterial HTRA. Four human HTRA members have been described: HTRA1-4. HTRA1 and HTRA3 share a high degree of domain homologies and may therefore share a functional similarity. HTRA1 mRNA and protein is reported to be down-regulated in SV40-transformed cells, a malignant melanoma cell line, ovarian tumors, and ovarian cancer cell lines, suggesting a progressive loss of HTRA1 and the protein in cancer. This raises the possibility that HTRA3 may likewise be involved in cancer. This study examined the expression of mRNA and protein levels of HTRA1 and HTRA3 in human endometrial cancer (EC).Methods. Reverse transcriptase-polymerase chain reaction (RT-PCR) analysis was performed in normal endometrium (n = 4) and in three grades of EC (n = 5 for each EC grade). Immunohistochemistry was used to determine the protein expression and the cellular localization of HTRA1 and HTRA3 in normal endometrium tissue (n = 6) and in three grades of EC (n = 8-10 for each EC grade).Results. RT-PCR analysis showed a significant reduction of HTRA1 and HTRA3 mRNA in endometrial cancer compared to normal endometrium. HTRA1 and HTRA3 protein showed a similar pattern of expression in EC tissue. Positive immunostaining, scored semiquantitatively, revealed a significant decrease of HTRA1 and 3 protein expression with increasing grades of EC.Conclusion. These data suggest that HTRA1 and HTRA3 mRNA and protein levels decrease with increasing grades of EC. (c) 2006 Elsevier Inc. All rights reserved.