caa a22 4500 445797932 CHVBK 20180317145132.0 cr unu---uuuuu 170323e20111101xx s 000 0 eng 10.1007/s10620-011-1734-7 doi (NATIONALLICENCE)springer-10.1007/s10620-011-1734-7 Epigenetic Inactivation of the SFRP1 Gene in Esophageal Squamous Cell Carcinoma [Elektronische Daten] [Ying Meng, Qing-Gang Wang, Jun-Xiong Wang, Sheng-tao Zhu, Yue Jiao, Peng Li, Shu-tian Zhang] Introduction: The secreted frizzled-related protein 1 (SFRP1) gene, as a Wnt signaling modulator, is frequently inactivated by promoter methylation in many tumors including gastric cancer, breast cancer, oral squamous cell carcinoma, and esophageal adenocarcinoma. However, the role of SFRP1 in esophageal squamous cell carcinoma (ESCC) is not clear. In this study, we investigated the epigenetic inactivation of the SFRP1 gene in ESCC. Methods: Nine ESCC cell lines, two immortalized human esophageal epithelial cell lines, twenty ESCC tissues, and paired adjacent nontumor tissues were analyzed in the study. Methylation-specific polymerase chain reaction (PCR), bisulfite sequencing, reverse-transcription PCR, immunohistochemistry, and chromatin immunoprecipitation assay were used to detect SFRP1 promoter methylation, expression of the SFRP1 gene, and histone modification in the SFRP1 promoter region. Results: The SFRP1 promoter was found to be highly methylated in 95% (19/20) of the ESCC tissues and in nine ESCC cell lines, compared with 65% (13/20) of the paired nontumor tissues. Moreover, we confirmed that complete methylation of the SFRP1 gene promoter was correlated with its greatly reduced expression level. After individual treatment with 5-aza-2′-deoxycytidine (DAC) and trichostatin A (TSA), the messenger RNA (mRNA) level of the SFRP1 gene was not obviously rescued in the EC9706 cell line. Combined incubation with DAC and TSA can, however, substantially increase the SFRP1 mRNA expression level in the EC9706 cell line. Chromatin immunoprecipitation assay showed that acetylated histone H3 and H4 were found in the SFRP1 promoter region. Conclusion: Promoter hypermethylation of SFRP1 is a frequent event in ESCC. Promoter methylation and histone acetylation may cooperatively regulate expression of the SFRP1 gene. Springer Science+Business Media, LLC, 2011 Esophageal squamous cell carcinoma nationallicence DNA methylation nationallicence SFRP1 nationallicence Acetylation nationallicence Meng Ying Department of Gastroenterology, Beijing Friendship Hospital Affiliated to the Capital Medical University, 95 Yong'an Road, 100050, Beijing, China aut Wang Qing-Gang Department of Gastroenterology, Beijing Friendship Hospital Affiliated to the Capital Medical University, 95 Yong'an Road, 100050, Beijing, China aut Wang Jun-Xiong Department of Gastroenterology, Beijing Friendship Hospital Affiliated to the Capital Medical University, 95 Yong'an Road, 100050, Beijing, China aut Zhu Sheng-tao Department of Gastroenterology, Beijing Friendship Hospital Affiliated to the Capital Medical University, 95 Yong'an Road, 100050, Beijing, China aut Jiao Yue Department of Gastroenterology, Beijing Friendship Hospital Affiliated to the Capital Medical University, 95 Yong'an Road, 100050, Beijing, China aut Li Peng Department of Gastroenterology, Beijing Friendship Hospital Affiliated to the Capital Medical University, 95 Yong'an Road, 100050, Beijing, China aut Zhang Shu-tian Department of Gastroenterology, Beijing Friendship Hospital Affiliated to the Capital Medical University, 95 Yong'an Road, 100050, Beijing, China aut Digestive Diseases and Sciences Springer US; http://www.springer-ny.com 56/11(2011-11-01), 3195-3203 0163-2116 56:11<3195 2011 56 10620 https://doi.org/10.1007/s10620-011-1734-7 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s10620-011-1734-7 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Meng Ying Department of Gastroenterology, Beijing Friendship Hospital Affiliated to the Capital Medical University, 95 Yong'an Road, 100050, Beijing, China aut NATIONALLICENCE 700 1- Wang Qing-Gang Department of Gastroenterology, Beijing Friendship Hospital Affiliated to the Capital Medical University, 95 Yong'an Road, 100050, Beijing, China aut NATIONALLICENCE 700 1- Wang Jun-Xiong Department of Gastroenterology, Beijing Friendship Hospital Affiliated to the Capital Medical University, 95 Yong'an Road, 100050, Beijing, China aut NATIONALLICENCE 700 1- Zhu Sheng-tao Department of Gastroenterology, Beijing Friendship Hospital Affiliated to the Capital Medical University, 95 Yong'an Road, 100050, Beijing, China aut NATIONALLICENCE 700 1- Jiao Yue Department of Gastroenterology, Beijing Friendship Hospital Affiliated to the Capital Medical University, 95 Yong'an Road, 100050, Beijing, China aut NATIONALLICENCE 700 1- Li Peng Department of Gastroenterology, Beijing Friendship Hospital Affiliated to the Capital Medical University, 95 Yong'an Road, 100050, Beijing, China aut NATIONALLICENCE 700 1- Zhang Shu-tian Department of Gastroenterology, Beijing Friendship Hospital Affiliated to the Capital Medical University, 95 Yong'an Road, 100050, Beijing, China aut NATIONALLICENCE 773 0- Digestive Diseases and Sciences Springer US; http://www.springer-ny.com 56/11(2011-11-01), 3195-3203 0163-2116 56:11<3195 2011 56 10620 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer