Airway basal cells of healthy smokers express an embryonic stem cell signature relevant to lung cancer. Academic Article uri icon

Overview

MeSH

  • Adenocarcinoma
  • Animals
  • Cell Line, Tumor
  • Epithelium
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Mice
  • Multivariate Analysis
  • Phenotype
  • Proportional Hazards Models
  • Survival Analysis
  • Tumor Suppressor Protein p53

MeSH Major

  • Embryonic Stem Cells
  • Gene Expression Profiling
  • Lung
  • Lung Neoplasms
  • Smoking

abstract

  • Activation of the human embryonic stem cell (hESC) signature genes has been observed in various epithelial cancers. In this study, we found that the hESC signature is selectively induced in the airway basal stem/progenitor cell population of healthy smokers (BC-S), with a pattern similar to that activated in all major types of human lung cancer. We further identified a subset of 6 BC-S hESC genes, whose coherent overexpression in lung adenocarcinoma (AdCa) was associated with reduced lung function, poorer differentiation grade, more advanced tumor stage, remarkably shorter survival, and higher frequency of TP53 mutations. BC-S shared with hESC and a considerable subset of lung carcinomas a common TP53 inactivation molecular pattern which strongly correlated with the BC-S hESC gene expression. These data provide transcriptome-based evidence that smoking-induced reprogramming of airway BC toward the hESC-like phenotype might represent a common early molecular event in the development of aggressive lung carcinomas in humans. © AlphaMed Press.

publication date

  • September 2013

has subject area

  • Adenocarcinoma
  • Animals
  • Cell Line, Tumor
  • Embryonic Stem Cells
  • Epithelium
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Lung
  • Lung Neoplasms
  • Mice
  • Multivariate Analysis
  • Phenotype
  • Proportional Hazards Models
  • Smoking
  • Survival Analysis
  • Tumor Suppressor Protein p53

Research

keywords

  • Journal Article

Identity

Language

  • eng

PubMed Central ID

  • PMC4051142

Digital Object Identifier (DOI)

  • 10.1002/stem.1459

PubMed ID

  • 23857717

Additional Document Info

start page

  • 1992

end page

  • 2002

volume

  • 31

number

  • 9