Monoallelic up-regulation of the imprinted H19 gene in airway epithelium of phenotypically normal cigarette smokers. Academic Article uri icon

Overview

MeSH

  • Adult
  • Alleles
  • Female
  • Humans
  • Male
  • Oligonucleotide Array Sequence Analysis
  • RNA, Long Noncoding
  • RNA, Messenger
  • Up-Regulation

MeSH Major

  • Bronchi
  • Genomic Imprinting
  • RNA, Untranslated
  • Respiratory Mucosa
  • Smoking

abstract

  • H19, a paternally imprinted gene, is postulated to have regulatory functions in normal development and oncogenesis. Loss of imprinting (LOI) of H19 is observed in human malignancies, including lung cancer. Microarray assessment of gene expression patterns in airway epithelium of healthy 20 pack-year smokers versus nonsmokers revealed that smokers have dramatically elevated H19 RNA levels without alteration of expression of other imprinted genes. Interestingly, the up-regulation of H19 was not attributable to LOI, i.e., expression of H19 in smokers was monoallelic. These observations suggest that cigarette smoking initially induces up-regulation of the active H19 allele and that there is likely progression to LOI as the burden of smoking increases and as the epithelium undergoes transition from normal to neoplastic. Overexpression and eventual LOI of H19 may represent early markers in the progression of airway epithelium toward lung cancer.

publication date

  • April 1, 2003

has subject area

  • Adult
  • Alleles
  • Bronchi
  • Female
  • Genomic Imprinting
  • Humans
  • Male
  • Oligonucleotide Array Sequence Analysis
  • RNA, Long Noncoding
  • RNA, Messenger
  • RNA, Untranslated
  • Respiratory Mucosa
  • Smoking
  • Up-Regulation

Research

keywords

  • Journal Article

Identity

Language

  • eng

PubMed ID

  • 12670893

Additional Document Info

start page

  • 1475

end page

  • 1482

volume

  • 63

number

  • 7