Environmental exposure and HPV infection may act synergistically to induce lung tumorigenesis in nonsmokers

Ya Wen Cheng, Frank Cheau Feng Lin, Chih Yi Chen, Nan Yung Hsu

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Most studies of lung tumorigenesis have focused on smokers rather than nonsmokers. In this study, we used human papillomavirus (HPV)-positive and HPV-negative lung cancer cells to test the hypothesis that HPV infection synergistically increases DNA damage induced by exposure to the carcinogen benzo[a]pyrene (B[a]P), and contributes to lung tumorigenesis in nonsmokers. DNA adduct levels induced by B[a]P in HPV-positive cells were significantly higher than in HPV-negative cells. The DNA adduct formation was dependent on HPV E6 oncoprotein expression. Gene and protein expression of two DNA repair genes, XRCC3 and XRCC5, were lower in B[a]P-treated E6-positive cells than in E6-negative lung cancer cells. The reduced expression was also detected immunohistochemically and was caused by increased promoter hypermethylation. Moreover, mutations of p53 and epidermal growth factor receptor (EGFR) genes in lung cancer patients were associated with XRCC5 inactivation. In sum, our study indicates that HPV E6-induced promoter hypermethylation of the XRCC3 and XRCC5 DNA repair genes and the resultant decrease in their expression increases B[a]P-induced DNA adducts and contributes to lung tumorigenesis in nonsmokers.

Original languageEnglish
Pages (from-to)19850-19862
Number of pages13
JournalOncotarget
Volume7
Issue number15
DOIs
Publication statusPublished - Apr 12 2016

Fingerprint

Papillomavirus Infections
Environmental Exposure
Carcinogenesis
Lung
Benzo(a)pyrene
Lung Neoplasms
DNA Adducts
DNA Repair
erbB-1 Genes
Oncogene Proteins
Carcinogens
Genes
DNA Damage
Gene Expression
Mutation

Keywords

  • B[a]P
  • DNA repair
  • Environmental exposure
  • HPV
  • Promoter hypermethylation

ASJC Scopus subject areas

  • Oncology

Cite this

Environmental exposure and HPV infection may act synergistically to induce lung tumorigenesis in nonsmokers. / Cheng, Ya Wen; Lin, Frank Cheau Feng; Chen, Chih Yi; Hsu, Nan Yung.

In: Oncotarget, Vol. 7, No. 15, 12.04.2016, p. 19850-19862.

Research output: Contribution to journalArticle

Cheng, Ya Wen ; Lin, Frank Cheau Feng ; Chen, Chih Yi ; Hsu, Nan Yung. / Environmental exposure and HPV infection may act synergistically to induce lung tumorigenesis in nonsmokers. In: Oncotarget. 2016 ; Vol. 7, No. 15. pp. 19850-19862.
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