Identification of regulatory factors of neuroendocrine features in lung cancers

2017 Fiscal Year Final Research Report

• Project/Area Number: 15K19438
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Respiratory organ internal medicine
• Research Institution: Chiba Cancer Center (Research Institute)
• Principal Investigator: Suenaga Yusuke 千葉県がんセンター(研究所), がんゲノムセンター, 研究員 (80581793)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: 小細胞肺癌 / 神経内分泌 / 下垂体 / ホルモン / 転写因子 / 分化 / 脱分化 / 発生

Outline of Final Research Achievements

Small cell lung carcinoma (SCLC) shows neuroendocrine differentiation and highly expresses anterior pituitary hormones. Expression levels of adrenocorticotropic hormone in SCLC are associated with poor prognosis; however, mechanisms behind the hormone secretion in lung cancer cells have remained elusive. Here we show that transcription factors required for anterior pituitary development are activated during carcinogenesis of SCLCs. We compared the somatic mutations found in 346 adenocarcinomas and 77 SCLCs, and defined SCLC-specific mutations. The SCLC-specific mutations were enriched in downstream target genes of transcription factors related to anterior pituitary development. Furthermore, 3D culture of SCLC cell lines induced neuronal differentiation and promoted production of adrenocorticotropic hormone. Therefore, lung cancer cells use the developmental pathway of pituitary gland to show neuroendocrine differentiation.

Free Research Field

分子腫瘍学