Significance of epiregulin expression induced by KRAS or EGFR mutation in non-small-cell lung cancer

2013 Fiscal Year Final Research Report

• Project/Area Number: 23591134
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Respiratory organ internal medicine
• Research Institution: Gunma University
• Principal Investigator: SUNAGA NORIAKI 群馬大学, 医学部附属病院, 助教 (70400778)
• Project Period (FY): 2011 – 2013
• Keywords: 非小細胞肺癌 / KRAS遺伝子変異 / 分子標的治療

Research Abstract

EREG is overexpressed in non-small-cell lung cancers (NSCLCs) harboring KRAS, BRAF or EGFR mutations compared with small-cell lung cancers (SCLCs) or NSCLCs with wild-type KRAS/BRAF/EGFR. EREG expression was reduced by knockdown of mutant KRAS, BRAF or EGFR or by MEK or ERK inhibition in NSCLC cells. EREG expression positively correlated with KRAS copy number in KRAS-mutant NSCLCs. EREG was predominantly expressed in NSCLC tumors with pleural involvement, lymphatic permeation or vascular invasion and in KRAS-mutant adenocarcinomas. EREG expression is an independent prognostic marker and EREG overexpression along with KRAS mutations correlated with an unfavorable prognosis for lung adenocarcinoma patients. In KRAS-mutant and EREG overexpressing NSCLCs, EREG attenuation suppressed tumor growth and induced apoptosis. These results suggest that oncogenic KRAS-induced EREG overexpression contributes to an aggressive phenotype and could be a therapeutic target in oncogenic KRAS-driven NSCLC.

Research Products

• [Journal Article] Oncogenic KRAS-induced epiregulin overexpression contributes to aggressive phenotype and is a promising therapeutic target in non-small-cell lung cancer (2013)
  • Author(s): Noriaki Sunaga, Kyoichi Kaira, Hisao Imai, Kimihiro Shimizu, Tetsuhiro Nakano, David S Shames, Luc Girard, Junichi Soh, Mitsuo Sato, Yasuki Iwasaki, Tamotsu Ishizuka, Adi F. Gazdar, John D Minna, Masatomo Mori
  • Journal Title: Oncogene Volume: 32 Pages: 4034-4042
  • DOI: 10.1038/onc.2012.402
  • Peer Reviewed
• [Presentation] Clinicopathological and biological significance of epiregulin expression in non-small cell lung cancer (2013)
  • Author(s): 砂長則明
  • Organizer: 15th World Conference on Lung Cancer
  • Place of Presentation: Sydney, Australia
  • Year and Date: 2013-10-28
• [Presentation] 非小細胞肺癌におけるエピレグリンの臨床的及び分子生物学的意義 (2013)
  • Author(s): 砂長則明
  • Organizer: 第53回日本呼吸器学会学術講演会
  • Place of Presentation: 東京
  • Year and Date: 2013-04-20
• [Presentation] 非小細胞肺癌においてKRAS変異により誘導されるepiregulin過剰発現の予後因子及び治療標的としての可能性 (2012)
  • Author(s): 砂長則明
  • Organizer: 第53回日本肺癌学会総会
  • Place of Presentation: 岡山
  • Year and Date: 2012-11-08
• [Presentation] 非小細胞肺癌においてKRAS変異により誘導されるepiregulin過剰発現の意義 (2012)
  • Author(s): 砂長則明
  • Organizer: 第71回日本癌学会学術総会
  • Place of Presentation: 札幌
  • Year and Date: 2012-09-19
• [Presentation] 非小細胞肺癌におけるepiregulin過剰発現の意義 (2012)
  • Author(s): 砂長則明
  • Organizer: 第52回日本呼吸器学会学術講演会
  • Place of Presentation: 神戸
  • Year and Date: 2012-04-22