Molecular pathological analyses of proneural/neuroendocrine phenotype-obtaining mechanisms on lung cancer cells

2014 Fiscal Year Final Research Report

• Project/Area Number: 24590428
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Human pathology
• Research Institution: Chiba University (2014); Kyorin University (2012-2013)
• Principal Investigator: YAZAWA Takuya 千葉大学, 医学(系)研究科(研究院), 准教授 (50251054)
• Co-Investigator(Kenkyū-buntansha): SATO Hanako 聖マリアンナ医科大学, 医学部, 助教 (60438132) ; HARA Yukiko 杏林大学, 医学部, 講師 (40313267) ; SHIMOYAMADA Hiroaki 杏林大学, 医学部, 講師 (60381472) ; FUJIWARA Masachika 杏林大学, 医学部, 講師 (20407026) ; KAMMA Hiroshi 杏林大学, 医学部, 教授 (10195191)
• Research Collaborator: ISHII Jun ; SAKAEDA Masashi
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: 肺癌 / 神経内分泌癌 / 小細胞肺癌 / 大細胞神経内分泌癌 / カルチノイド腫瘍 / 分化形質 / 転写因子 / POU

Outline of Final Research Achievements

One-third of lung malignancies demonstrate a proneural/neuroendocrine phenotype, and lung cancers having a proneural/neuroendocrine phenotype reveal poor prognosis. However, it has not been elucidated how a proneural/neuroendocrine differentiation is controlled in lung cancers. Therefore, we conducted molecular pathological analyses of proneural/neuroendocrine phenotype-obtaining mechanisms on lung cancer cells, focusing upon homeobox gene expression. Small cell lung cancer cells specifically expressed LHX2, LHX6, and class III/IV POU transcription factors. Among them, class III/IV POU transcription factors could induce proneural and neuroendocrine marker genes, and especially, POU3F4 and POU4F2 could effectively be transformed large cell carcinoma cells into neuroendocrine cancer cells. These findings suggested that POU3F4 and POU4F2 play crucial roles on obtaining proneural-neuroendocrine phenotype in lung cancers.

Free Research Field

人体病理学