Benzo[a]pyrene promotes proliferation of human lung cancer cells by accelerating the epidermal growth factor receptor signaling pathway

Takuro Kometani, Ichiro Yoshino, Naoko Miura, Hiroshi Okazaki, Taro Oba, Tomoyoshi Takenaka, Fumihiro Shoji, Tokujiro Yano, Yoshihiko Maehara

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46 Citations (Scopus)


Smoking is an independent prognostic factor of lung adenocarcinoma. Benzo[a]pyrene (B[a]P) is one of the strongest carcinogens and it is present in both the environment and cigarette smoke. In this study, the effect of B[a]P on the proliferative activity of lung adenocarcinoma cells was investigated. A lung adenocarcinoma cell line, A549, was cultured with B[a]P for various periods, and its proliferative activity was examined by an MTS assay. To investigate the intracellular events related to the proliferative activity, the gene expression profile was investigated by a microarray analysis and a quantitative RT-PCR, and the protein expression and activation status of Akt, ERK 1/2 and the epidermal growth factor receptor (EGFR) were examined by a western blot analysis. Following the culture with B[a]P for 24 weeks, the serum-independent proliferative activity was increased. A microarray analysis revealed that a reversible upregulation of the EGFR and epiregulin genes was recognized in the B[a]P treated cells, in which the overexpression of the phosphorylated EGFR protein was also recognized. The EGFR tyrosine kinase inhibitor reduced the cellular proliferation and the level of phosphorylation of ERK1/2, which is a downstream signal of the EGFR, in the B[a]P-treated A549 cells. Moreover, the B[a]P treatment increased the mRNA expressions of the ligands for EGFR such as amphiregulin and epiregulin. B[a]P increases the proliferative potential of lung adenocarcinoma cells through the EGFR signaling pathway.

Original languageEnglish
Pages (from-to)27-33
Number of pages7
JournalCancer Letters
Issue number1
Publication statusPublished - Jun 8 2009

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research


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