Class III/IV POU transcription factors expressed in small cell lung cancer cells are involved in proneural/neuroendocrine differentiation. (September 2014)

• Record Type: Journal Article
• Authors: Ishii, Jun; Sato, Hanako; Yazawa, Takuya; Shishido‐Hara, Yukiko; Hiramatsu, Chie; Nakatani, Yukio; Kamma, Hiroshi
• Is Part Of: Pathology international. Volume 64:Number 9(2014:Sep.)
• Page Start: 415
• Page End: 422
• Publication Date: 2014-09
• Subjects: Pathology -- Periodicals; 616.07
• DOI: 10.1111/pin.12198
• Languages: English
• ISSNs: 1320-5463

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <p>One‐third of lung malignancies demonstrate a proneural/neuroendocrine phenotype or type of differentiation. However, it has not been clearly elucidated how proneural/neuroendocrine differentiation is controlled in lung cancers. We recently demonstrated that the <italic>POU3F2</italic> gene plays a significant role in proneural/neuroendocrine differentiation of lung cancers. Because <italic>class III POU</italic> genes (<italic>POU3F1</italic>, <italic>POU3F2, POU3F3</italic>, and <italic>POU3F4</italic>) and <italic>class IV POU</italic> genes (<italic>POU4F1</italic>, <italic>POU4F2</italic>, and <italic>POU4F3</italic>) share similar properties in neural development, we analyzed the association between <italic>class III/IV POU</italic> genes and a proneural/neuroendocrine phenotype in lung cancers using seven small cell lung cancer (SCLC) cell lines and twelve non‐SCLC (NSCLC) cell lines. <italic>Class III/IV POU</italic> gene expression was generally restricted to SCLC cells. However, the forced expression of <italic>class III/IV POU</italic> genes in the NSCLC cell lines induced the expression of neuroendocrine‐specific markers (neural call adhesion molecule 1, synaptophysin, and chromogranin A) and proneural transcription factors (achaete‐scute homolog‐like 1, NeuroD1, and thyroid transcription factor 1) in various degrees. Furthermore, each <italic>class III/IV POU</italic> gene induced other <italic>class III/IV POU</italic> genes, suggesting the mutual induction of <italic>class III/IV POU</italic> genes. These findings suggest that the expression of <italic>class III/IV POU</italic> genes is important for the proneural/neuroendocrine differentiation of lung cancer cells.</p> </abstract>