Epigenetic inactivation of SFRP genes in oral squamous cell carcinoma

  • Authors:
    • Yohei Sogabe
    • Hiromu Suzuki
    • Minoru Toyota
    • Kazuhiro Ogi
    • Takashi Imai
    • Masanori Nojima
    • Yasushi Sasaki
    • Hiroyoshi Hiratsuka
    • Takashi Tokino
  • View Affiliations

  • Published online on: June 1, 2008     https://doi.org/10.3892/ijo.32.6.1253
  • Pages: 1253-1261
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Abstract

Although mutations of APC, CTNNB1 (β-catenin) and AXIN1 are rare in oral squamous cell carcinoma (OSCC), activation of the Wnt signaling pathway is thought to play an important role in oral carcinogenesis. In the present study, we examined the relationship between Wnt signaling and epigenetic alteration of the secreted frizzled-related protein (SFRP) genes in OSCC. We frequently detected loss of membrane localization of β-catenin and its cytoplasmic or nuclear accumulation in OSCC cell lines, although these cell lines showed no APC or CTNNB1 (β-catenin) mutations and no methylation of CDH1 (E-cadherin). By contrast, we frequently detected methylation of SFRP1 (7/17, 41%) SFRP2 (16/17, 94%) and SFRP5 (14/17, 82%) in a panel of OSCC cell lines, as well as in specimens of primary tumors collected from 44 OSCC patients (SFRP1, 10/42, 24%; SFRP2, 16/44, 36%; SFRP5, 7/43, 16%). We also observed that OSCC cell lines express various Wnt ligands, and that ectopic expression of SFRPs inhibited cancer cell proliferation. Our results confirm the frequent methylation and silencing of SFRP genes in OSCC, and suggest that their loss of function contributes to activation of Wnt signaling that leads to cell proliferation during oral carcinogenesis.

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June 2008
Volume 32 Issue 6

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Sogabe Y, Suzuki H, Toyota M, Ogi K, Imai T, Nojima M, Sasaki Y, Hiratsuka H and Tokino T: Epigenetic inactivation of SFRP genes in oral squamous cell carcinoma. Int J Oncol 32: 1253-1261, 2008
APA
Sogabe, Y., Suzuki, H., Toyota, M., Ogi, K., Imai, T., Nojima, M. ... Tokino, T. (2008). Epigenetic inactivation of SFRP genes in oral squamous cell carcinoma. International Journal of Oncology, 32, 1253-1261. https://doi.org/10.3892/ijo.32.6.1253
MLA
Sogabe, Y., Suzuki, H., Toyota, M., Ogi, K., Imai, T., Nojima, M., Sasaki, Y., Hiratsuka, H., Tokino, T."Epigenetic inactivation of SFRP genes in oral squamous cell carcinoma". International Journal of Oncology 32.6 (2008): 1253-1261.
Chicago
Sogabe, Y., Suzuki, H., Toyota, M., Ogi, K., Imai, T., Nojima, M., Sasaki, Y., Hiratsuka, H., Tokino, T."Epigenetic inactivation of SFRP genes in oral squamous cell carcinoma". International Journal of Oncology 32, no. 6 (2008): 1253-1261. https://doi.org/10.3892/ijo.32.6.1253