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Cigarette smoke induces promoter methylation of single‐stranded DNA‐binding protein 2 in human esophageal squamous cell carcinoma
Author(s) -
Huang Yiping,
Chang Xiaofei,
Lee Juna,
Cho Yong Gu,
Zhong Xiaoli,
Park IlSeok,
Liu JunWei,
Califano Joseph A.,
Ratovitski Edward A.,
Sidransky David,
Kim Myoung Sook
Publication year - 2010
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.25569
Subject(s) - wnt signaling pathway , dna methylation , carcinogenesis , cancer research , cell culture , methylation , epigenetics , promoter , biology , downregulation and upregulation , microbiology and biotechnology , cell , gene expression , gene , signal transduction , genetics
Abstract Esophageal squamous cell carcinoma (ESCC) is the sixth most frequent cause of cancer death in the world, and cigarette smoke is a key factor in esophageal carcinogenesis. To identify molecular changes during cigarette smoke‐induced ESCC, we examined the methylation status of 13 gene promoters in the human immortalized, nontumorigenic esophageal epithelial cell line (Het‐1A) that were exposed to mainstream (MSE) or sidestream cigarette smoke extract (SSE) for 6 months in culture. The promoter of sequence‐specific single‐stranded DNA‐binding protein 2 ( SSBP2 ) was methylated in the Het‐1A cells exposed to MSE (MSE‐Het‐1A). Promoter methylation (86%, 56/70) and downregulation of SSBP2 expression were frequently detected in tumor tissues from ESCC patients. In addition, reintroduction of SSBP2 in an ESCC cell line (TE1) that does not express SSBP2 and in the MSE‐Het‐1A cells inhibited expression of LRP6 and Dvl3, which are mediators of the Wnt signaling pathway. SSBP2 expression markedly decreased the colony‐forming ability of ESCC cell lines and significantly inhibited cell growth of the MSE‐Het‐1A cells. Our results indicate that cigarette smoking is a cause of SSBP2 promoter methylation and that SSBP2 harbors a tumor suppressive role in ESCC through inhibition of the Wnt signaling pathway.