| Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2016: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2015: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
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| 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.
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