Oestrogen receptor‐mediated expression of Olfactomedin 4 regulates the progression of endometrial adenocarcinoma

Chao Duan,Zheng Yang,Xubin Liu,Li Yu,Meng Xia,Shuang Liang,Shangwu Chen,Liantang Wang

doi:10.1111/jcmm.12232

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.

Highlights

Olfactomedin 4 (OLFM4), designated as human granulocyte colonystimulating factor-stimulated clone 1 [1] or GW112 [2], is mainly expressed in the digestive system, prostate and bone marrow
OLFM4 was identified by digital differential display (DDD) as a differentially expressed gene associated with differentiation of endometrial adenocarcinoma
To explore the genes that might contribute to tumour differentiation, three UniGene libraries derived respectively from well, moderately- and poorly-differentiated endometrial adenocarcinomas were subjected to DDD analysis

Summary

Introduction

Olfactomedin 4 (OLFM4), designated as human granulocyte colonystimulating factor-stimulated clone 1 (hGC-1) [1] or GW112 [2], is mainly expressed in the digestive system, prostate and bone marrow. Aberrant expression of OLFM4 has been detected in several types of tumours, especially of the digestive system [3, 4]. OLFM4 expression is enhanced in gastric cancer (GC), with 56% of GC cases positive for OLFM4 [3, 5]. Increased expression of OLFM4 was observed in peripheral blood mononuclear cells of pancreatic adenocarcinoma patients [8]. Expression of OLFM4 is low or absent in poorly differentiated or undifferentiated gastric and colon cancers and enhanced in more differentiated cancers [3, 4]. Olfactomedin 4 expression is down-regulated in advanced gastric and colon cancers [4, 5]. OLFM4 may be a marker for stem cells in human intestine and for a subset of colorectal a 2014 The Authors

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