Reprogramming of epidermal keratinocytes and the process of tumorigenesis

• Project/Area Number: 16K10159
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Dermatology
• Research Institution: The University of Tokushima
• Principal Investigator: KUBO Yoshiaki 徳島大学, 大学院医歯薬学研究部(医学域), 教授 (10260069)
• Co-Investigator(Kenkyū-buntansha): 松立 吉弘 徳島大学, 病院, 講師 (80622729)
• Project Period (FY): 2016-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2016: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 表皮細胞 / 腫瘍化プロセス / リプログラミング / 日光角化症 / Bowen病 / ボーエン病 / 腫瘍化 / 腫瘍内不均一性 / 有棘細胞癌

Outline of Final Research Achievements

Proteins were extracted from 2 frozen samples of actinic keratosis (AK) and Bowen's disease (BD), and a total of 701 proteins were identified using liquid chromatography-mass spectrometry. Twelve proteins highly expressed in each of AK and BD were identified, and among them, RCE1, CDC42, 14-3-3 beta, and 14-3-3 zeta in AK and DUSP1, PEDF, and PTRF in BD were selected. Immunostaining with each antibody was performed using AK and BD specimens, but it was not possible to identify molecules with distinctly different expression in tumor cells between AK and BD. It is considered that protein expression analysis by mass spectrometry using a frozen sample of intraepithelial cancer did not function sufficiently effectively.

Academic Significance and Societal Importance of the Research Achievements

皮膚癌は欧米の白人のみならず、日本においても患者数は増加傾向にあり、皮膚表皮細胞の腫瘍化プロセスを詳細に検討することは、学術的にも社会的にも意義がある。本研究では、皮膚癌の早期病変である表皮内癌の日光角化症とボーエン病において、網羅的なタンパク質発現解析を行った。研究期間中には各腫瘍細胞において発現が明らかに異なる分子を同定することはできなかったが、各病態に関与の可能性がある新規因子を複数同定することができた。今後の発癌分子機構解明や発癌予防に向けて一役を担えるものと考える。