Monoallelic up-regulation of the imprinted H19 gene in airway epithelium of phenotypically normal cigarette smokers

Rana Kaplan, Karsta Luettich, Adriana Heguy, Neil R. Hackett, Ben Gary Harvey, Ronald Crystal

Research output: Contribution to journalArticle

45 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1475-1482
Number of pages8
JournalCancer Research
Volume63
Issue number7
Publication statusPublished - 1 Apr 2003
Externally publishedYes

Fingerprint

Tobacco Products
Up-Regulation
Epithelium
Genes
Lung Neoplasms
Smoking
Carcinogenesis
Alleles
Gene Expression
Imprinting (Psychology)
Neoplasms

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Kaplan, R., Luettich, K., Heguy, A., Hackett, N. R., Harvey, B. G., & Crystal, R. (2003). Monoallelic up-regulation of the imprinted H19 gene in airway epithelium of phenotypically normal cigarette smokers. Cancer Research, 63(7), 1475-1482.

Monoallelic up-regulation of the imprinted H19 gene in airway epithelium of phenotypically normal cigarette smokers. / Kaplan, Rana; Luettich, Karsta; Heguy, Adriana; Hackett, Neil R.; Harvey, Ben Gary; Crystal, Ronald.

In: Cancer Research, Vol. 63, No. 7, 01.04.2003, p. 1475-1482.

Research output: Contribution to journalArticle

Kaplan, R, Luettich, K, Heguy, A, Hackett, NR, Harvey, BG & Crystal, R 2003, 'Monoallelic up-regulation of the imprinted H19 gene in airway epithelium of phenotypically normal cigarette smokers', Cancer Research, vol. 63, no. 7, pp. 1475-1482.
Kaplan, Rana ; Luettich, Karsta ; Heguy, Adriana ; Hackett, Neil R. ; Harvey, Ben Gary ; Crystal, Ronald. / Monoallelic up-regulation of the imprinted H19 gene in airway epithelium of phenotypically normal cigarette smokers. In: Cancer Research. 2003 ; Vol. 63, No. 7. pp. 1475-1482.
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