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Effects of silencing of HER2/neu gene in anti-BPDE-transformed cells

Yiguo Jiang1, Juan Fu, Anne R Greenlee

  • 1Institute for Chemical Carcinogenesis, State Key Laboratory of Respiratory Diseases, Guangzhou Medical College, 195 Dongfengxi Road, Guangzhou 510182, China. jiangyiguo@yahoo.com

Toxicology in Vitro : an International Journal Published in Association with BIBRA
|November 11, 2008
PubMed

Insights

Anti-benzo[a]pyrene-7,8-diol-9,10-epoxide (anti-BPDE), a potent mutagen, transforms bronchial cells. Inhibiting HER2/neu in these cells impacted cell cycle, viability, and colony formation, suggesting its oncogenic role in anti-BPDE carcinogenesis.

Area of Science:

  • Environmental Toxicology
  • Molecular Carcinogenesis
  • Cell Biology

Background:

  • Anti-benzo[a]pyrene-7,8-diol-9,10-epoxide (anti-BPDE) is a potent mutagen derived from benzo[a]pyrene (B[a]P).
  • The molecular mechanisms underlying anti-BPDE-induced carcinogenesis remain largely uncharacterized.
  • Overexpression of HER2/neu was previously observed in anti-BPDE-transformed human bronchial epithelial cells (16HBE-T).

Purpose of the Study:

  • To investigate the role of HER2/neu in the biological phenotype of 16HBE-T cells transformed by anti-BPDE.
  • To elucidate the molecular mechanisms of anti-BPDE-induced carcinogenesis by targeting HER2/neu.

Main Methods:

  • Utilized malignant human bronchial epithelial cells (16HBE-T) exposed to anti-BPDE.
  • Employed RNA interference, specifically retrovirus-delivered short hairpin RNA (shRNA), to silence HER2/neu expression in vitro.
  • Analyzed cell cycle distribution, cell viability, and colony formation rates.

Main Results:

  • Silencing HER2/neu significantly increased the proportion of cells in the G0/G1 phase (67.1+/-2.1%).
  • HER2/neu inhibition led to a significant decrease in the proportion of cells in S phase (17.3+/-4.1%).
  • Reduced cell viability and colony formation rates were observed following HER2/neu silencing.

Conclusions:

  • HER2/neu plays a significant role in the altered biologic phenotype of anti-BPDE-transformed bronchial epithelial cells.
  • The findings suggest an oncogenic role for HER2/neu in the process of anti-BPDE-induced carcinogenesis.
  • This study provides insights into epithelial cell transformation following exposure to the environmental mutagen anti-BPDE.

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