Cigarette smoke induces promoter methylation of single-stranded DNA-binding protein 2 in human esophageal squamous cell carcinoma

Yiping Huang, Xiaofei Chang, Juna Lee, Yong Gu Cho, Xiaoli Zhong, Il Seok Park, Jun Wei Liu, Joseph A. Califano, Edward A. Ratovitski, David Sidransky, Myoung Sook Kim

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)2261-2273
Number of pages13
JournalInternational Journal of Cancer
Volume128
Issue number10
DOIs
StatePublished - May 1 2011

Fingerprint

DNA-Binding Proteins
Smoke
Tobacco Products
Methylation
Wnt Signaling Pathway
Cell Line
Neoplasms
Aptitude
human SSBP2 protein
Esophageal Squamous Cell Carcinoma
Cause of Death
Carcinogenesis
Down-Regulation
Smoking
Epithelial Cells
Growth
Genes

Keywords

  • cigarette smoking
  • ESCC
  • promoter methylation
  • SSBP2

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Cigarette smoke induces promoter methylation of single-stranded DNA-binding protein 2 in human esophageal squamous cell carcinoma. / Huang, Yiping; Chang, Xiaofei; Lee, Juna; Cho, Yong Gu; Zhong, Xiaoli; Park, Il Seok; Liu, Jun Wei; Califano, Joseph A.; Ratovitski, Edward A.; Sidransky, David; Kim, Myoung Sook.

In: International Journal of Cancer, Vol. 128, No. 10, 01.05.2011, p. 2261-2273.

Research output: Contribution to journalArticle

Huang, Y, Chang, X, Lee, J, Cho, YG, Zhong, X, Park, IS, Liu, JW, Califano, JA, Ratovitski, EA, Sidransky, D & Kim, MS 2011, 'Cigarette smoke induces promoter methylation of single-stranded DNA-binding protein 2 in human esophageal squamous cell carcinoma', International Journal of Cancer, vol. 128, no. 10, pp. 2261-2273. https://doi.org/10.1002/ijc.25569
Huang, Yiping ; Chang, Xiaofei ; Lee, Juna ; Cho, Yong Gu ; Zhong, Xiaoli ; Park, Il Seok ; Liu, Jun Wei ; Califano, Joseph A. ; Ratovitski, Edward A. ; Sidransky, David ; Kim, Myoung Sook. / Cigarette smoke induces promoter methylation of single-stranded DNA-binding protein 2 in human esophageal squamous cell carcinoma. In: International Journal of Cancer. 2011 ; Vol. 128, No. 10. pp. 2261-2273.
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