DNA hypomethylation at the CpG island is involved in aberrant expression of the L1 cell adhesion molecule gene in colorectal cancer

Kuniyuki Kato, Chihaya Maesawa, Tetsuya Itabashi, Kentaro Fujisawa, Koki Otsuka, Shoji Kanno, Hiroshi Tada, Yoshinori Tatemichi, Koji Kotani, Hiroki Oikawa, Tamotsu Sugai, Go Wakabayashi, Tomoyuki Masuda

Research output: Contribution to journalArticlepeer-review

15 Citations (Scopus)

Abstract

The L1 cell adhesion molecule (L1CAM) has been identified as a target gene of β-catenin-TCF signaling in colorectal cancer (CRC) and associated with aggressive tumor behavior such as invasion and metastasis. We investigated the methylation status at the L1CAM gene promoter and/or L1CAM mRNA/protein expression in 4 CRC cell lines and 71 primary CRCs. Aberrant L1CAM expression was immunohistochemically observed in 31 (43.7%) of 71 cases, and correlated with advanced stage and presence of lymph node and distant metastases (P<0.05). Treatment with a demethylating agent induced L1CAM mRNA/protein expression in two cell lines lacking L1CAM expression. Bisulfite-modified genome sequencing suggested that DNA methylation status at core promoter and putative TCF-binding sites within the L1CAM promoter was correlated with L1CAM mRNA/protein expression in 4 CRC cell lines. Using the crypt isolation followed by bisulfite-modified genome sequencing and methylation-specific PCR methods, we confirmed that the DNA hypomethylation at core promoter and putative TCF-binding sites was well correlated with the aberrant L1CAM protein expression in primary CRC samples. These results suggest that DNA hypomethylation at the L1CAM CpG islands might induce L1CAM aberrant expression and contribute to the acquisition of aggressive tumor behavior in CRC.

Original languageEnglish
Pages (from-to)467-476
Number of pages10
JournalInternational journal of oncology
Volume35
Issue number3
DOIs
Publication statusPublished - 2009
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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