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POU domain transcription factor BRN 2 is crucial for expression of ASCL 1, ND 1 and neuroendocrine marker molecules and cell growth in small cell lung cancer
Author(s) -
Ishii Jun,
Sato Hanako,
Sakaeda Masashi,
ShishidoHara Yukiko,
Hiramatsu Chie,
Kamma Hiroshi,
Shimoyamada Hiroaki,
Fujiwara Masachika,
Endo Tetsuya,
Aoki Ichiro,
Yazawa Takuya
Publication year - 2013
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.12042
Subject(s) - pou domain , neural cell adhesion molecule , synaptophysin , chromogranin a , biology , population , transcription factor , cancer research , cell , neuroendocrine differentiation , microbiology and biotechnology , cell adhesion , immunohistochemistry , medicine , cancer , gene , immunology , genetics , environmental health , prostate cancer , homeobox
BRN2 is a developmental neural cell‐specific POU domain transcription factor and is crucial for cell lineage determination. We investigated the importance of BRN 2 in the expression of the lineage‐specific transcription factors (achaete‐scute homolog‐like 1 ( ASCL 1) and N euro D 1 ( ND 1)) and neural/neuroendocrine marker molecules (neural cell adhesion molecule 1 ( NCAM 1), synaptophysin ( SYP ) and chromogranin A ( CHGA )) in small cell lung cancer ( SCLC ) using cultured lung cancer cells. All examined SCLC cell lines expressed BRN 2, as well as ASCL 1, ND 1, NCAM 1, SYP and CHGA . The expression levels of ASCL 1, ND 1, NCAM 1, SYP and CHGA considerably decreased when BRN 2 was knocked down in SCLC cells, and the addition of a BRN 2 transgene into non‐ SCLC ( NSCLC ) cells induced the expression of ASCL 1, ND 1, NCAM 1, SYP and CHGA . However, the BRN 2 gene was not activated by the forced expression of ASCL 1 or ND 1 in NSCLC cells. The knockdown of BRN 2 caused significant growth retardation with decrease of S to G 2 phase population and mitotic cell rates and unaltered K i‐67‐labeled or apoptotic cell rates in SCLC cells, indicating increase of G 1 phase population. These findings suggest that BRN 2 is a higher level regulator than ASCL 1 and ND 1 and BRN 2 might be involved in aggressiveness of SCLC .