PES1 differentially regulates the expression of ERα and ERβ in ovarian cancer

Abstract

Estrogen exhibits mitogenic activity in early ovarian carcinogenesis and plays an important role in ovarian tumorigenesis. Due to the increased expression of ERa and decreased expression of the ERb, the ratio of ERa and ERb is markedly increased in ovarian cancer. We have recently reported that PES1 regulates the balance of ERa and ERb at the posttranscriptional level in breast cancer. Here, we report that PES1 inversely regulates the expression of ERa and ERb in addition to their transcriptional activities in epithelial ovarian cancer. We found that the ablation of PES1 resulted in the significant downregulation of ERa and estrogen-responsive genes such as cylin D1, HIF-1a and VEGF and the up-regulation of ERb and p21WAF1. Cell proliferation in both tested ovarian cell lines was markedly inhibited and cells were arrested in G2 after PES1 was ablated. Further analysis of clinical samples showed that expression of PES1 correlated positively with ERa expression and negatively with ERb expression. Our results demonstrate that PES1 may play important role in the progression of ovarian cancer by inversely regulating the ERa and ERb expression. PES1 may be a new target for ovarian cancer therapy.

PES1 is overexpressed in Hepatocellular Carcinoma

“…Our results showed that ablation of PES1 differentially regulated p21WAF1 and Cyclin D1 expression and resulted in G1 phase arrest in HCC cells which was in concern with other researchers' results in other kinds of cancer cells [22,25]. However, repression of PES1 could result in G2 phase arrest in ovarian cancer cells and gastric cancer cells [23,25]. So it may be very interesting to investigate the precise mechanisms of cell cycle regulated by PES1.…”

“…It has been shown that pescadillo could immortalize or transform some kinds of mammalian cells [15,16]. Our previous researches and other investigators' researches showed that PES1 was overexpressed in many kinds of human cancer such as malignant astrocytomas and glioblastomas [6], breast cancer [16][17][18], prostatic cancer [19,20], head and neck squamous cell cancer [21], colon cancer [22], ovarian cancer [23], neuroblastoma [24] and gastric cancer [25]. These results suggest that PES1 may play an important role in tumor progression.…”

Repression of PES1 expression inhibits growth of gastric cancer

“…Anchorage-dependent growth was analyzed as described [25]. Cells were plated on 24-well plates (2×10 2 cells per well) and cultured for 2 weeks.…”

“…We have recently reported that PES1 promoted tumorigenesis of breast cancer and ovarian cancer cells by increasing tumor-promoting estrogen receptor α (ERα) expression and decreasing tumor-suppressive ERβ expression [21,25]. Moreover, PES1 was found to function as an oncogene in colon cancer cells; ablation of PES1 in colon cancer cells resulted in decreased proliferation and reduced growth of xenografts [24].…”

“…Furthermore, it has been shown that alteration of PES1 expression could cause chromosomal instability which contributed to carcinogenesis and immortalized or transformed some kinds of mammalian cells [17,18]. In addition, PES1 was found to be overexpressed in several kinds of human cancers, such as malignant astrocytomas and glioblastomas [4], breast cancer [19][20][21], prostatic carcinoma [22,23], head and neck squamous cell carcinomas [13], colon cancer [24], ovarian cancer [25], and neuroblastoma [26]. These researches suggest that PES1 may play an important role in tumor progression.…”