Abstract

Although PARP1 promoter methylation is involved in the regulation of PARP1 expression in human keratinocyte lines and lymphoblastoid cell lines, its roles in human endometrial cancer are unknown. DNA from forty normal endometrium (NE) and fifty endometrial adenocarcinoma (EAC) tissues were analyzed by bisulfite sequencing using primers focusing on the core promoter region of PARP1. Expression levels of PARP1 were assessed by immunohistochemistry and real-time PCR. Associations between patient clinicopathological characteristics and PARP1 protein levels were assessed by Fisher's exact test. Here, PARP1 mRNA and protein were overexpressed in EAC tissues (P < 0.05). CpG sites within the ETS motif in the PARP1 promoter exhibited significant hypomethylation in EAC tissues, and there was a significant negative correlation between PARP1 mRNA levels and the number of methylated sites in both NE and EAC tissues (R 2 = 0.262, P < 0.001). Notably, PARP1 protein expression was associated with FIGO stage (P = 0.026), histological grade (P = 0.002) , and body mass index (P = 0.04). Our findings imply that PARP1 overexpression may participate in endometrial cancer progression, and abnormal hypomethylation of CpG sites within the ETS motif in the core promoter region may be responsible for PARP1 overexpression in EAC tissues.

Highlights

  • Endometrial cancer (EC) is the most common gynecologic malignancy in the United States [1], but the molecular mechanisms involved in EC initiation and progression remain largely unknown

  • poly-(ADP-ribose) polymerase 1 (PARP1) Expression Was Upregulated in endometrial adenocarcinoma (EAC) Tissues

  • Realtime PCR and immunohistochemical analysis showed that PARP1 mRNA and protein were overexpressed in EAC tissues compared to normal endometrium (NE) tissues (P < 0.05; Figures 1(a) and 1(b))

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Summary

Introduction

Endometrial cancer (EC) is the most common gynecologic malignancy in the United States [1], but the molecular mechanisms involved in EC initiation and progression remain largely unknown. The expression of PARP1 gradually increases in each stage of EC, which is highly correlated with progesterone receptor levels [3]. It is conceivable that PARP1 plays an important role in the development of EC through its involvement in regulating progesterone receptor expression. Recent studies have suggested that PARP1 promoter methylation is involved in the regulation of PARP1 expression in human keratinocyte lines [4] and lymphoblastoid cell lines [5]. Our present study is the first to analyze DNA methylation patterns in the core promoter region of PARP1, showing that the abnormal methylation patterns, especially around the E26 transformation-specific (ETS) motif, may be responsible for PARP1 overexpression in EC. Correlation of PARP1 expression with clinicopathological characteristics was analyzed

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