Document Detail


Differences of molecular expression mechanisms among neural cell adhesion molecule 1, synaptophysin, and chromogranin A in lung cancer cells.
MedLine Citation:
PMID:  22449227     Owner:  NLM     Status:  In-Data-Review    
Abstract/OtherAbstract:
Neural cell adhesion molecule 1 (NCAM1), synaptophysin (SYPT), and chromogranin A (CGA) are immunohistochemical markers for diagnosing lung neuroendocrine tumors (LNETs). However, the precise expression mechanisms have not been studied in enough detail. The purpose of the present study is to define the molecular mechanisms of NCAM1, SYPT, and CGA gene expressions, using cultivated lung cancer cells and focusing upon NeuroD1 (ND1), achaete-scute homolog-like 1 (ASCL1), and known transcription factors, repressor element 1 (RE1)-silencing transcription factor (REST) and c-AMP responsive element-binding protein (CREB). Promoter assays, chromatin immunoprecipitation, and transfection experiments revealed that ND1 activated NCAM1, that ASCL1 weakly upregulated SYPT expression, and that CGA expression was not regulated by ND1 or ASCL1. REST expression was restricted in non-small cell lung cancer (NSCLC) cells, and knockdown of REST could cause as much SYPT expression as in SCLC cells and weak CGA expression in NSCLC cells. However, CGA gene upregulation via CREB activation was not found in REST-lacking NSCLC cells, indicating the requirement of some additional mechanism for sufficient expression. These results suggest that NCAM1, SYPT and CGA expressions are differently regulated by neuroendocrine phenotype-specific transcription factors and provide a reason why NCAM1 and SYPT are frequently expressed in LNETs, irrespective of malignancy grade.
Authors:
Korehito Kashiwagi; Jun Ishii; Masashi Sakaeda; Yuu Arimasu; Hiroaki Shimoyamada; Hanako Sato; Chie Miyata; Hiroshi Kamma; Ichiro Aoki; Takuya Yazawa
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Publication Detail:
Type:  Journal Article     Date:  2012-01-13
Journal Detail:
Title:  Pathology international     Volume:  62     ISSN:  1440-1827     ISO Abbreviation:  Pathol. Int.     Publication Date:  2012 Apr 
Date Detail:
Created Date:  2012-03-27     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9431380     Medline TA:  Pathol Int     Country:  Australia    
Other Details:
Languages:  eng     Pagination:  232-45     Citation Subset:  IM    
Copyright Information:
© 2011 The Authors. Pathology International © 2011 Japanese Society of Pathology and Blackwell Publishing Asia Pty Ltd.
Affiliation:
Department of Pathology, Yokohama City University Graduate School of Medicine, Yokohama Department of Pathology, Kyorin University School of Medicine, Mitaka Department of Anatomy, St. Marianna University School of Medicine, Kawasaki, Japan.
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