title: Abnormal Localization and Tumor Suppressor Function of Epithelial Tissue-Specific Transcription Factor ESE3 in Esophageal Squamous Cell Carcinoma.
abstract: Esophageal cancer is one of the most common malignant cancers worldwide. The molecular mechanism of esophageal squamous cell carcinoma (ESCC) is still poorly understood. ESE3 is a member of the Ets transcription family, which is only expressed in epithelial tissues and acts as a tumor suppressor gene in prostate cancer. Our study aim was to confirm whether ESE3 is involved in the carcinogenesis of ESCC. Immunohistochemical analysis revealed that ESE3 was mainly located in cell nuclei of normal tissues and the cytoplasm in ESCC tissues. Immunofluorescence and western blot analyses of the normal esophageal cell line HEEpiC and ESCC cell lines EC9706 TE-1, KYSE150, and KYSE410 confirmed these results. pEGFP-ESE3 and pcDNA3.1-V5/HisA-ESE3 plasmids were constructed for overexpression of ESE3 in EC9706 and KYSE150 cells. The stably transfected cells showed restoration of the nuclear localization of ESE3. EC9706 cells with re-localization of ESE3 to the nucleus showed inhibition of proliferation, colony formation, migration, and invasion. To explore the possible mechanism of the differences in localization of ESE3 in normal esophageal cells and ESCC cells, ESCC cell lines were treated with the nuclear export inhibitor leptomycin B, transcription inhibitor actinomycin D, PKC inhibitor sphinganine, P38 MAPK inhibitor SB202190, and CK II inhibitor TBCA. These reagents were chosen according to the well-known mechanisms of protein translocation. However, the localization of ESE3 was unchanged after these treatments. The sequence of ESE3 cDNA in ESCC cells was identical to the standard sequence of ESE3 in the NCBI Genebank database, indicating that there was no mutation in the coding region of ESE3 in ESCC. Taken together, our study suggests that ESE3 plays an important role in the carcinogenesis of ESCC through changes in subcellular localization and may act as a tumor suppressor gene in ESCC, although the mechanisms require further study.
authors.affiliation: Department of Gastroenterology & Hepatology, Beijing Digestive Disease Center, Beijing Friendship Hospital, Capital Medical University, National Clinical Research Center for Digestive Diseases, Beijing Key Laboratory for Precancerous Lesion of Digestive Diseases, Beijing, China.
authors.forename: Li
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Gastroenterology & Hepatology, Beijing Digestive Disease Center, Beijing Friendship Hospital, Capital Medical University, National Clinical Research Center for Digestive Diseases, Beijing Key Laboratory for Precancerous Lesion of Digestive Diseases, Beijing, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Xing
authors.affiliation: Department of Gastroenterology & Hepatology, Beijing Digestive Disease Center, Beijing Friendship Hospital, Capital Medical University, National Clinical Research Center for Digestive Diseases, Beijing Key Laboratory for Precancerous Lesion of Digestive Diseases, Beijing, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Cheng
authors.affiliation: Department of Gastroenterology & Hepatology, Beijing Digestive Disease Center, Beijing Friendship Hospital, Capital Medical University, National Clinical Research Center for Digestive Diseases, Beijing Key Laboratory for Precancerous Lesion of Digestive Diseases, Beijing, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Shao
authors.affiliation: Department of Gastroenterology & Hepatology, Beijing Digestive Disease Center, Beijing Friendship Hospital, Capital Medical University, National Clinical Research Center for Digestive Diseases, Beijing Key Laboratory for Precancerous Lesion of Digestive Diseases, Beijing, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Li
authors.affiliation: Department of Gastroenterology & Hepatology, Beijing Digestive Disease Center, Beijing Friendship Hospital, Capital Medical University, National Clinical Research Center for Digestive Diseases, Beijing Key Laboratory for Precancerous Lesion of Digestive Diseases, Beijing, China.
authors.forename: Shengtao
authors.initials: S
authors.lastname: Zhu
authors.affiliation: Department of Gastroenterology & Hepatology, Beijing Digestive Disease Center, Beijing Friendship Hospital, Capital Medical University, National Clinical Research Center for Digestive Diseases, Beijing Key Laboratory for Precancerous Lesion of Digestive Diseases, Beijing, China.
authors.forename: Shutian
authors.initials: S
authors.lastname: Zhang
mesh_terms: D021581:Active Transport, Cell Nucleus; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D002465:Cell Movement; D002467:Cell Nucleus / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D049109:Cell Proliferation; D004848:Epithelium / Q000378:metabolism / Q000473:pathology*; D004938:Esophageal Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D000077277:Esophageal Squamous Cell Carcinoma; D004947:Esophagus / Q000378:metabolism / Q000473:pathology*; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; D006801:Humans; D009361:Neoplasm Invasiveness / Q000235:genetics / Q000473:pathology; D014157:Transcription Factors / Q000032:analysis* / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation
chemical_list: C403306:EHF protein, human; D014157:Transcription Factors