Identification of a novel tumor-suppressor gene through methylome analysis in smoking-associated lung adenocarcinoma

• Project/Area Number: 25861245
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Respiratory surgery
• Research Institution: The University of Tokushima
• Principal Investigator: KAJIURA Koichiro 徳島大学, 大学病院, 助教 (60596253)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2014: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2013: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
• Keywords: 肺腺癌 / エピゲノム / メチル化 / 喫煙

Outline of Final Research Achievements

We explored aberrant DNA methylation of lung adenocarcinoma possible to be induced by smoking with surgical specimen. Comprehensive analysis of epigenome alternation showed TRIM58 gene was hypermethylation on promotor region in cancer tissue significantly. It is tendency that hypermethylation in smoker cohort compare to non-smoker cohort. Pyrosequencing showed similar result. Real time RT-PCR showed mRNA expression is lower in cancer tissue than in normal tissue significantly. Immunostaining showed protein expression level is lower in cancer tissue than in normal tissue. We transfected TRIM58 in A549 . Cell count and MTT assay showed cell growth inhabitation in A549 transfected TRIM58. We transplanted this A549 cell line to subcutaneous in SCID mice, The growth of A549 transfected TRIM58 was inhibited significantly. TRIM58 is thoughtto be tumor suppressor gene and inactivated by DNA methylation.

Research Products

• [Presentation] Identification of a novel tumor-suppressor gene through methylome analysis in smoking-associated lung adenocarcinoma (2013)
  • Author(s): 梶浦耕一郎、井本逸勢、増田清士、田嶋 敦、近藤和也、丹黒 章
  • Organizer: 第72回日本癌学会学術総会
  • Place of Presentation: パシフィコ横浜（神奈川県横浜市）