SIRT1 in B[a]P-induced lung tumorigenesis

Oncotarget. 2015 Sep 29;6(29):27113-29. doi: 10.18632/oncotarget.4729.

Abstract

Benzo[a]pyrene (B[a]P) is a carcinogen in cigarette smoke. We found that B[a]P induced SIRT1 in human bronchial epithelial BEAS-2B cell. SIRT1 was overexpressed in the lung of B[a]P-exposed mice and in human lung cancer biopsies. SIRT1 up-regulated TNF-α and β-catenin and down-regulated the membrane fraction of E-cadherin. In addition, SIRT1 promoted invasion, migration and tumorigenesis of BEAS-2B cells in nude mice upon B[a]P exposure. Thus, SIRT1 is involved in B[a]P-induced transformation associated with activation of the TNF-α/β-catenin axis and is as a potential therapeutic target for lung cancer.

Keywords: B[a]P; SIRT1; TNF-α; lung cancer; β-catenin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Benzo(a)pyrene / chemistry*
  • Biopsy
  • Bronchi / pathology
  • Carcinogenesis / metabolism
  • Cell Line, Tumor
  • Cell Movement
  • Cell Transformation, Neoplastic / metabolism
  • Epithelial Cells / metabolism
  • Female
  • Humans
  • Lung / pathology
  • Lung Neoplasms / chemically induced*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Nude
  • Neoplasm Invasiveness
  • Sirtuin 1 / metabolism*
  • Smoking / adverse effects
  • Transcription, Genetic
  • Tumor Necrosis Factor-alpha / metabolism*
  • Up-Regulation
  • beta Catenin / metabolism*

Substances

  • Tumor Necrosis Factor-alpha
  • beta Catenin
  • Benzo(a)pyrene
  • SIRT1 protein, human
  • Sirtuin 1