Epidermal growth factor signals regulate dihydropyrimidine dehydrogenase expression in EGFR-mutated non-small-cell lung cancer

2016 Fiscal Year Final Research Report

• Project/Area Number: 26462130
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Respiratory surgery
• Research Institution: Nagasaki University
• Principal Investigator: NAGAYASU Takeshi 長崎大学, 医歯薬学総合研究科(医学系), 教授 (80284686)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: 非小細胞肺癌 / Sp1 / DPD / EGFR

Outline of Final Research Achievements

It has been shown that EGFR mutation status is associated with 5-FU sensitivity in non-small-cell lung cancer (NSCLC). However, the relationship between EGFR
mutation status and DPD, a 5-FU degrading enzyme, is unknown. In EGFR mutated cell, EGF treatment induced up-regulation of both Sp1 and DPD. EGFR-TKI and mithramycin A, a specific Sp-1 inhibitor, suppressed them. EGFR-TKI inhibited DPD protein expression only in EGFR-mutated cell lines. FU treatment decreased the level of cell viability more in gefitinib-treated EGFR-TKI sensitive cell lines. Further, combination treatment of FU and mithramycin A suppressed cell viability even in a gefitinib resistant cell line. The EGFR signal cascade regulates DPD expression via Sp1 in EGFR mutant cells. These results might be a step towards new therapies targeting Sp1 and DPD in NSCLC with different EGFR mutant status.

Free Research Field

腫瘍外科学