Bowden Marissa A, Di Nezza-Cossens Lisa A, Jobling Tom, Salamonsen Lois A, Nie Guiying
Prince Henry's Institute of Medical Research, P.O. Box 5152, Clayton, Victoria 3168, Australia.
Gynecol Oncol. 2006 Oct;103(1):253-60. doi: 10.1016/j.ygyno.2006.03.006. Epub 2006 May 2.
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).
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).
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.
These data suggest that HTRA1 and HTRA3 mRNA and protein levels decrease with increasing grades of EC.
高温需求因子A（HTRA）家族由丝氨酸蛋白酶组成，其结构域与细菌HTRA的结构域同源。已描述了四个人类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，HTRA1 mRNA和蛋白在SV40转化细胞、恶性黑色素瘤细胞系、卵巢肿瘤和卵巢癌细胞系中表达下调，提示在癌症中HTRA1及其蛋白逐渐缺失。这增加了HTRA3同样可能参与癌症发生的可能性。本研究检测了人子宫内膜癌（EC）中HTRA1和HTRA3的mRNA和蛋白水平表达情况。
对正常子宫内膜（n = 4）和三个级别的EC（每个EC级别n = 5）进行逆转录聚合酶链反应（RT-PCR）分析。采用免疫组织化学方法确定HTRA1和HTRA3在正常子宫内膜组织（n = 6）和三个级别的EC（每个EC级别n = 8 - 10）中的蛋白表达及细胞定位。
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组织中呈现相似的表达模式。半定量评分的阳性免疫染色显示，随着EC级别的增加，HTRA1和3蛋白表达显著降低。
这些数据表明，随着EC级别的增加，HTRA1和HTRA3的mRNA和蛋白水平降低。
