Arecoline-regulated ataxia telangiectasia mutated expression level in oral cancer progression

Hsi Feng Tu, Michael Yuanchien Chen, Joseph Chieh Yui Lai, Yi Ling Chen, Yih Wen Wong, Cheng Chieh Yang, Hsin Yuan Chen, Shih Min Hsia, Yin Hwa Shih, Tzong Ming Shieh

Research output: Contribution to journalArticlepeer-review

21 Citations (Scopus)


Background: Ataxia telangiectasia mutated (ATM) regulates DNA repair and cell cycle. The present study analyzed arecoline-induced ATM expression during oral cancer progression. Methods: In vitro studies were performed using oral squamous cell carcinoma (OSCC) cell lines treated with arecoline to analyze cell response and ATM regulation. in vivo studies were performed using immunohistochemistry to detect ATM expression in normal, oral potentially malignant disorder (OPMD), and OSCC tissues. Results: Low-dose arecoline induced cell proliferation, ATM promoter activity, and DNA repair. High-dose arecoline induced cell cycle arrest, apoptosis, and DNA damage. ATM was overexpressed in OPMD tissues but was downregulated in OSCC tissues. ATM expression level was associated with the risk of developing dysplasia, buccal-OSCC, and with OSCC survival rate. Conclusion: High ATM expression helps DNA repair mechanisms to maintain the cells in the OPMD stage, but low ATM expression causes DNA damage accumulation to increase cell malignancy.

Original languageEnglish
Pages (from-to)2525-2537
Number of pages13
JournalHead and Neck
Issue number8
Publication statusPublished - Aug 2019


  • arecoline
  • ataxia telangiectasia mutated (ATM)
  • DNA repair
  • oral potentially malignant disorder (OPMD)
  • oral squamous cell carcinoma (OSCC)

ASJC Scopus subject areas

  • Otorhinolaryngology


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