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Class III / IV POU transcription factors expressed in small cell lung cancer cells are involved in proneural/neuroendocrine differentiation
Author(s) -
Ishii Jun,
Sato Hanako,
Yazawa Takuya,
ShishidoHara Yukiko,
Hiramatsu Chie,
Nakatani Yukio,
Kamma Hiroshi
Publication year - 2014
Publication title -
pathology international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.73
H-Index - 74
eISSN - 1440-1827
pISSN - 1320-5463
DOI - 10.1111/pin.12198
Subject(s) - pou domain , biology , neuroendocrine differentiation , cancer research , transcription factor , gene , cancer , genetics , homeobox , prostate cancer
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 POU3F2 gene plays a significant role in proneural/neuroendocrine differentiation of lung cancers. Because class III POU genes ( POU3F1 , POU3F2 , POU3F3 , and POU3F4 ) and class IV POU genes ( POU4F1 , POU4F2 , and POU4F3 ) share similar properties in neural development, we analyzed the association between class III / IV POU 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. Class III / IV POU gene expression was generally restricted to SCLC cells. However, the forced expression of class III / IV POU 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, Neuro D 1, and thyroid transcription factor 1) in various degrees. Furthermore, each class III / IV POU gene induced other class III / IV POU genes, suggesting the mutual induction of class III / IV POU genes. These findings suggest that the expression of class III / IV POU genes is important for the proneural/neuroendocrine differentiation of lung cancer cells.