Abstract

Endometrial cancer is one of the most common malignancies in the female genital tract. Programmed cell death 5 (PDCD5) is a newly identified apoptosis related gene and plays an important role in the development of some human tumors. However, the expression and clinical significance of PDCD5 in endometrial cancer have not been fully elucidated. Here, we evaluated the expression of PDCD5 in endometrioid endometrial carcinoma and control endometrium by qRT-PCR, western blot and immunohistochemistry, and analyzed the associations of PDCD5 expression with clinicopathological parameters of patients. In addition, we detected the expression of PDCD5 in control endometrial glandular epithelial cells and endometrioid endometrial carcinoma-derived cell line KLE by immunocytochemistry. The results showed that PDCD5 protein mainly expressed in the cytoplasm of glandular epithelial cells and endometrial carcinoma cells, and there was a low level of PDCD5 expression in the nuclei of the above cells. Furthermore, PDCD5 protein level was significantly lower in endometrial carcinoma samples than that in control endometrium. The decreased PDCD5 expression was correlated with the tumor differentiation degree. It is clear that PDCD5 protein expression was lower in middle and low differentiated endometrial carcinoma compared with control endometrium and high differentiated endometrial carcinoma. However, there were no significant differences of PDCD5 expression between the proliferative phase and the secretory phase of control endometrium, as well as between high differentiated endometrial carcinoma and controls. The results were verified in control glandular epithelial cells and KLE cells by immunocytochemistry. Therefore, PDCD5 may play a key role in the pathogenesis of endometrial cancer and may be a novel target for diagnosis and treatment of endometrial cancer.

Highlights

  • Programmed cell death 5 (PDCD5) is a novel apoptosis accelerating gene which was first identified from the leukaemic cell clone TF-1 cells undergoing apoptosis in Human Disease Gene Center of Peking University.it is called TF-1 cell apoptosis-related gene 19 (TFAR19) (Liu et al 1999)

  • The expression levels of PDCD5 mRNA in control endometrium and endometrioid endometrial carcinoma tissues detected by quantitative real‐time PCR (qRT‐PCR) In order to study the roles of PDCD5 in endometrioid endometrial carcinoma, we firstly detected PDCD5 mRNA expression in freshly frozen endometrioid endometrial carcinoma tissues and control endometrium using quantitative real-time polymerase chain reaction (qRT-PCR)

  • The data showed that the expression of PDCD5 protein in endometrioid endometrial carcinoma tissues was significantly lower than that in control endometrium, which was inconsistent with the results of qRT-PCR (P < 0.001) (Fig. 2a, b)

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Summary

Introduction

Programmed cell death 5 (PDCD5) is a novel apoptosis accelerating gene which was first identified from the leukaemic cell clone TF-1 cells undergoing apoptosis in Human Disease Gene Center of Peking University. It is called TF-1 cell apoptosis-related gene 19 (TFAR19) (Liu et al 1999). It has been reported that PDCD5 promotes DNA damage-induced apoptosis by interacting with Tip (a histone acetyltransferase) (Xu et al 2009), and PDCD5 phosphorylation induced by a multifunctional kinase CK2 is an important process for its apoptotic potential (Salvi et al 2009). Park et al reported YY1-associated factor 2 (YAF2) interacts with PDCD5 and promotes TP53-mediated genotoxic stress response via stabilization of PDCD5. OTU deubiquitinase (OTUD5) binds to PDCD5 in response to etoposide treatment and effectively mediates the sequential activation of both

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