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Erk/MAP kinase signaling pathway and neuroendocrine differentiation of non-small-cell lung cancer.

Publication ,  Journal Article
Chen, Y; Nowak, I; Huang, J; Keng, PC; Sun, H; Xu, H; Wei, G; Lee, SO
Published in: J Thorac Oncol
January 2014

INTRODUCTION: Almost all small-cell lung cancers (SCLC) and carcinoid tumors express neuroendocrine differentiation (NED), and 10% to 20% of non-small-cell lung cancers (NSCLC) are associated with NED. Although distinct clinical features and histology of SCLC and carcinoid tumors are well recognized, the clinical significance and the molecular basis of NED in NSCLC remain unclear. METHODS: To explore the potential molecular pathway involved in NED of NSCLC and its clinical relevance, we conducted investigations using an NSCLC cell line (NCI-H157) as a NED induction model, and explored the potential intracellular signal transduction pathways involved in NED of NSCLC. We confirmed our findings using activators versus inhibitors to these signal transduction pathways in vitro. We also performed immunohistochemical stains of phospho-Erk1/2 of lung cancer specimens known to have NED and explored its clinical relevance. RESULTS: We discovered that NED of NSCLC was associated with the activation of Erk1/2-mitogen-activated protein kinases (MAPK) signal transduction pathway, and the inhibition of the Akt signal transduction pathway. Using specific activator (Pb) and inhibitors (siRNA-Erk1/2 and U0126) to the Erk1/2-MAP-kinase pathway, as well as the inhibitor (LY294002) to the Akt pathway, we found that Erk1/2-MAP-kinase activation was essential for NED of NCI-H157 cells. Staining of Erk1/2-MAP-kinase pathway revealed a high rate of positivity in NSCLC tumors with NED when compared with other neuroendocrine lung tumors. CONCLUSIONS: To our knowledge, our findings are the first to describe the potential involvement of Erk/MAPK signal transduction pathway of NSCLC in the association with NED. Further investigation of the Erk/MAPK signal transduction pathway of NSCLC may yield discoveries in identifying specific molecular targets for the treatment of NSCLC with NED.

Duke Scholars

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Published In

J Thorac Oncol

DOI

EISSN

1556-1380

Publication Date

January 2014

Volume

9

Issue

1

Start / End Page

50 / 58

Location

United States

Related Subject Headings

  • Proto-Oncogene Proteins c-akt
  • Phosphorylation
  • Phosphopyruvate Hydratase
  • Oncology & Carcinogenesis
  • Nitriles
  • Neurosecretory Systems
  • Mitogen-Activated Protein Kinase Kinases
  • MAP Kinase Signaling System
  • Lung Neoplasms
  • Lead
 

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Chen, Y., Nowak, I., Huang, J., Keng, P. C., Sun, H., Xu, H., … Lee, S. O. (2014). Erk/MAP kinase signaling pathway and neuroendocrine differentiation of non-small-cell lung cancer. J Thorac Oncol, 9(1), 50–58. https://doi.org/10.1097/JTO.0000000000000034
Chen, Yuhchyau, Irena Nowak, Jiaoti Huang, Peter C. Keng, Hongliang Sun, Haodong Xu, Gang Wei, and Soo Ok Lee. “Erk/MAP kinase signaling pathway and neuroendocrine differentiation of non-small-cell lung cancer.J Thorac Oncol 9, no. 1 (January 2014): 50–58. https://doi.org/10.1097/JTO.0000000000000034.
Chen Y, Nowak I, Huang J, Keng PC, Sun H, Xu H, et al. Erk/MAP kinase signaling pathway and neuroendocrine differentiation of non-small-cell lung cancer. J Thorac Oncol. 2014 Jan;9(1):50–8.
Chen, Yuhchyau, et al. “Erk/MAP kinase signaling pathway and neuroendocrine differentiation of non-small-cell lung cancer.J Thorac Oncol, vol. 9, no. 1, Jan. 2014, pp. 50–58. Pubmed, doi:10.1097/JTO.0000000000000034.
Chen Y, Nowak I, Huang J, Keng PC, Sun H, Xu H, Wei G, Lee SO. Erk/MAP kinase signaling pathway and neuroendocrine differentiation of non-small-cell lung cancer. J Thorac Oncol. 2014 Jan;9(1):50–58.
Journal cover image

Published In

J Thorac Oncol

DOI

EISSN

1556-1380

Publication Date

January 2014

Volume

9

Issue

1

Start / End Page

50 / 58

Location

United States

Related Subject Headings

  • Proto-Oncogene Proteins c-akt
  • Phosphorylation
  • Phosphopyruvate Hydratase
  • Oncology & Carcinogenesis
  • Nitriles
  • Neurosecretory Systems
  • Mitogen-Activated Protein Kinase Kinases
  • MAP Kinase Signaling System
  • Lung Neoplasms
  • Lead