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Oestrogen receptor‐mediated expression of Olfactomedin 4 regulates the progression of endometrial adenocarcinoma
Authors:Chao Duan  Xubin Liu  Shuang Liang  Zheng Yang  Meng Xia  Liantang Wang  Shangwu Chen  Li Yu
Institution:1. Department of Pathology, The First Affiliated Hospital, Sun Yat‐sen (Zhongshan) University, , Guangzhou, China;2. Gynecology and Obstetrics, The First Affiliated Hospital, Sun Yat‐sen (Zhongshan) University, , Guangzhou, China;3. State Key Laboratory for Biocontrol, Guangdong Key Laboratory of Pharmaceutical Functional Genes, Department of Biochemistry, School of Life Sciences, Sun Yat‐sen (Zhongshan) University, , Guangzhou, China
Abstract:Endometrial adenocarcinoma is the most common tumour of the female genital tract in developed countries, and oestrogen receptor (ER) signalling plays a pivotal role in its pathogenesis. When we used bioinformatics tools to search for the genes contributing to gynecological cancers, the expression of Olfactomedin 4 (OLFM4) was found by digital differential display to be associated with differentiation of endometrial adenocarcinoma. Aberrant expression of OLFM4 has been primarily reported in tumours of the digestive system. The mechanism of OLFM4 in tumuorigenesis is elusive. We investigated OLFM4 expression in endometrium, analysed the association of OLFM4 with ER signalling in endometrial adenocarcinoma, and examined the roles of OLFM4 in endometrial adenocarcinoma. Expression of OLFM4 was increased during endometrial carcinogenesis, linked to the differentiation of endometrioid adenocarcinoma, and positively related to the expression of oestrogen receptor‐α (ERα) and progesterone receptor. Moreover, ERα‐mediated signalling regulated expression of OLFM4, and knockdown of OLFM4 enhanced proliferation, migration and invasion of endometrial carcinoma cells. Down‐regulation of OLFM4 was associated with decreased cumulative survival rate of patients with endometrioid adenocarcinoma. Our data suggested that impairment of ERα signal‐mediated OLFM4 expression promoted the malignant progression of endometrioid adenocarcinoma, which may have significance for the therapy of this carcinoma.
Keywords:olfactomedin 4 (OLFM4)  endometrial adenocarcinoma  gynecological cancer  oestrogen receptor (ER)  endometrial hyperplasia
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