Transcriptional Regulation of PES1 Expression by c-Jun in Colon Cancer

Abstract

Pescadillo is a nucleolar protein that has been suggested to be involved in embryonic development and ribosome biogenesis. Deregulated expression of human pescadillo (PES1) was described in some tumors, but its precise roles in tumorigenesis remains unclear. In this study, we generated three monoclonal antibodies recognizing PES1 with high specificity and sensitivity, with which PES1 expression in human colon cancer was analyzed immunohistochemically. Out of 265 colon cancer tissues, 89 (33.6%) showed positive PES1 expression, which was significantly higher than in non-cancerous tissues (P<0.001). Silencing of PES1 in colon cancer cells resulted in decreased proliferation, reduced growth of xenografts, and cell cycle arrest in G1 phase, indicating PES1 functions as an oncogene. We then explored the mechanism by which PES1 expression is controlled in human colon cancers and demonstrated that c-Jun, but not JunB, JunD, c-Fos, or mutant c-Jun, positively regulated PES1 promoter transcription activity. In addition, we mapped −274/−264 region of PES1 promoter as the c-Jun binding sequence, which was validated by chromatin immunoprecipitation and electrophoretic mobility shift assays. Moreover, we demonstrated a positive correlation between c-Jun and PES1 expression in colon cancer cells and colon cancer tissues. Upstream of c-Jun, it was revealed that c-Jun NH2-terminal kinases (JNK) is essential for controlling PES1 expression. Our study, in the first place, uncovers the oncogenic role of PES1 in colon cancer and elucidates the molecular mechanism directing PES1 expression.

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].…”

“…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.…”

The Role of sLZIP in Transcriptional Regulation of c-Jun and Involvement in Migration and Invasion of Cervical Cancer Cells

“…Elevated c-Jun expression and AP-1 activity have been detected in various cancer types [11], and activation of AP-1 for regulation of targets occurs via c-Jun phosphorylation through the c-Jun activation signaling pathways [28]. c-Jun also interacts with other transcription factors to regulate their expression in many biological processes [11,35]. Therefore, regulation of c-Jun expression and c-Jun activation signaling is important in cancer development.…”

Repression of PES1 expression inhibits growth of gastric cancer

“…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.…”

“…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]. It was showed that messenger RNA (mRNA) level of PES1 was overexpressed in stomach cancer cells [27].…”