Serine proteases HTRA1 and HTRA3 are down-regulated with increasing grades of human endometrial cancer

Abstract

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.