Differences of molecular expression mechanisms among neural cell adhesion molecule 1, synaptophysin, and chromogranin A in lung cancer cells.

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.
AuthorsKorehito Kashiwagi, Jun Ishii, Masashi Sakaeda, Yuu Arimasu, Hiroaki Shimoyamada, Hanako Sato, Chie Miyata, Hiroshi Kamma, Ichiro Aoki, Takuya Yazawa
JournalPathology international (Pathol Int) Vol. 62 Issue 4 Pg. 232-45 (Apr 2012) ISSN: 1440-1827 [Electronic] Australia
PMID22449227 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
Copyright© 2011 The Authors. Pathology International © 2011 Japanese Society of Pathology and Blackwell Publishing Asia Pty Ltd.
Chemical References
  • ASCL1 protein, human
  • Antigens, CD56
  • Basic Helix-Loop-Helix Transcription Factors
  • CREB1 protein, human
  • Chromogranin A
  • Cyclic AMP Response Element-Binding Protein
  • NCAM1 protein, human
  • NEUROD1 protein, human
  • Neoplasm Proteins
  • RE1-silencing transcription factor
  • Repressor Proteins
  • SYP protein, human
  • Synaptophysin
  • Vesicular Transport Proteins
  • NADH Dehydrogenase
  • NADH dehydrogenase subunit 1, human
  • Antigens, CD56 (genetics, metabolism)
  • Basic Helix-Loop-Helix Transcription Factors (genetics, metabolism)
  • Carcinoma, Neuroendocrine (genetics, pathology)
  • Carcinoma, Non-Small-Cell Lung (genetics, pathology)
  • Cell Line, Tumor
  • Chromogranin A (genetics)
  • Cyclic AMP Response Element-Binding Protein (genetics, metabolism)
  • Gene Expression Regulation, Neoplastic
  • Gene Knockdown Techniques
  • HEK293 Cells
  • Humans
  • Lung Neoplasms (genetics, pathology)
  • NADH Dehydrogenase (genetics, metabolism)
  • Neoplasm Proteins (genetics, metabolism)
  • Repressor Proteins (genetics, metabolism)
  • Synaptophysin
  • Transfection
  • Vesicular Transport Proteins (genetics)

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