A study on the response of oral mucosa to reactive oxygen species and its application to the prevention against oral cancer.

2013 Fiscal Year Final Research Report

• Project/Area Number: 23390468
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Surgical dentistry
• Research Institution: Fukuoka Dental College
• Principal Investigator: IKEBE Tetsuro 福岡歯科大学, 歯学部, 教授 (20202913)
• Co-Investigator(Kenkyū-buntansha): HAYAKAWA Hiroshi 福岡歯科大学, 口腔歯学部, 教授 (70150422)
• Co-Investigator(Renkei-kenkyūsha): KAJIYA Hiroshi 福岡歯科大学, 口腔歯学部, 講師 (80177378)
• Project Period (FY): 2011-04-01 – 2014-03-31
• Keywords: 活性酸素 / 口腔癌 / ケラチノサイト / 細胞老化 / 癌抑制遺伝子 / エピジェネティック修飾

Research Abstract

In order to investigate the mechanism how reactive oxygen species (ROS) induce carcinogenesis of keratinocytes, normal human kerainocytes (NHEK) and oral squamous carcinoma cells (SCCs) were treated with hydrogen peroxide, and compared for the expressions of cellular senescence-associated molecules that is thought to be one of the tumor suppressor mechanisms. Hydrogen peroxide increased the expressions of senescence associated-beta-galactosidase and p16(INK4a) and induced the growth arrest in G0/G1 phase, in NHEK, but not SCC cells. Methylation level in p16 (INK4a) promoter was reduced with hydrogen peroxide in NHEK, but not SCCs. Methylation inhibitor 5-Azac enhanced the expression of p16 (INK4a) in NHEK, but not SCCs. The expression of DNA methyltransferase DNMT1 was suppressed in NHEK, but not SCCs. The inhibition of cellular senescence through the epigenetic modification on p16 (INK4a) expression may play an important role in carcinogenesis of keratinocytes.

Research Products

• [Journal Article] Pathophysiology of BRONJ : Drug-related osteoclastic disease of the jaw (2013)
  • Author(s): Ikebe T
  • Journal Title: Oral Science Int Volume: 10 Pages: 1-8
• [Journal Article] Inhibition of extracellular signal-regulated kinase downregulates claudin-2 expression and alters paracellular permeability in mouse rectum CMT93-II cells (2013)
  • Author(s): Inai T, Kitagawa N, Hatakeyama Y, Ikebe T, Iida H, Fujita M
  • Journal Title: Tissue and Cell Volume: 45(3) Pages: 175-182
• [Journal Article] Blockade of TRPM8 activity reduces the invasion potential of oral squamous carcinoma cell lines (2012)
  • Author(s): Okamoto Y, Ohkubo T, Ikebe T, Yamazaki J
  • Journal Title: Int J Oncol Volume: 40 Pages: 1431-1440
• [Journal Article] Reduced expression of nuclear factor kB in oral mucosa undergoing preoperative chemoradiotherapy (2012)
  • Author(s): Ikebe T, Yamasaki K, Takamune Y, Nakayama H, Shinohara M
  • Journal Title: Oral Science Int Volume: 9 Pages: 33-37
• [Journal Article] Reactive oxygen species stimulates epithelial mesenchymal transition in normal human epithelial keratinocytes via TGF-beta secretion (2012)
  • Author(s): Fukawa T, Kajiya H, Ozeki S, Ikebe T, Okabe K
  • Journal Title: Exp Cell Res Volume: 318 Pages: 1926-1932
• [Journal Article] Selective inhibition of nuclear factor-ĸB by nuclear factor-ĸB essential modulator-binding domain peptide suppresses the metastasis of highly metastatic oral squamous cell carcinoma (2012)
  • Author(s): Tanaka T, Nakayama H, Yoshitake Y, Irie A, Nagata M, Kawahara K, Takamune Y, Yoshida R, Nakagawa Y, Ogi H, Shinriki S, Ota K, Hiraki A, Ikebe T, Nishimura Y, Shinohara M
  • Journal Title: Cancer Sci Volume: 103 Pages: 455-463