Pb2+ induces gastrin gene expression by extracellular signal-regulated kinases 1/2 and transcription factor activator protein 1 in human gastric carcinoma cells

Authors

  • Chien-Pin Chan,

    1. Transplant Medicine and Surgery Research Centre, Department of General Surgery, Changhua Christian Hospital, Changhua, Taiwan
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  • Yao-Ting Tsai,

    1. Department of Clinical Pharmacy, School of Pharmacy, Taipei Medical University, Taipei, Taiwan
    2. Institute of Master Program for Clinical Pharmacogenomics and Pharmacoproteomics, School of Pharmacy, Taipei Medical University, Taipei, Taiwan
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  • Yao-Li Chen,

    1. Transplant Medicine and Surgery Research Centre, Changhua Christian Hospital, Changhua, Taiwan
    2. School of Medicine, Chung Shan Medical University, Taichung, Taiwan
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  • Yu-Wen Hsu,

    1. Department of Clinical Pharmacy, School of Pharmacy, Taipei Medical University, Taipei, Taiwan
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  • Joseph T. Tseng,

    1. Institute of Bioinformatics and Biosignal Transduction, College of Bioscience and Biotechnology, National Cheng Kung University, Tainan, Taiwan
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  • Hung-Yi Chuang,

    1. Department of Public Health, College of Health Sciences, Kaohsiung Medical University, Kaohsiung, Taiwan
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  • Robert Shiurba,

    1. Integrative Bioscience and Biomedical Engineering, Graduate School of Science and Engineering, Waseda University, Japan
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  • Mei-Hsien Lee,

    1. Graduate Institute of Pharmacognosy, College of Pharmacy, Taipei Medical University, Taipei, Taiwan
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  • Jaw-Yuan Wang,

    Corresponding author
    1. Department of Clinical Pharmacy, School of Pharmacy, Taipei Medical University, Taipei, Taiwan
    2. Cancer Center, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
    3. Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
    4. Division of Gastroenterologic and General Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
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  • Wei-Chiao Chang

    Corresponding author
    1. Department of Clinical Pharmacy, School of Pharmacy, Taipei Medical University, Taipei, Taiwan
    2. Cancer Center, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
    3. Department of Pharmacy, Taipei Medical University-Wanfang Hospital, Taipei, Taiwan
    4. Institute of Master Program for Clinical Pharmacogenomics and Pharmacoproteomics, School of Pharmacy, Taipei Medical University, Taipei, Taiwan
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ABSTRACT

Divalent lead ions (Pb2+) are toxic environmental pollutants known to cause serious health problems in humans and animals. Absorption of Pb2+ from air, water, and food takes place in the respiratory and digestive tracts. The ways in which absorbed Pb2+ affects cell physiology are just beginning to be understood at the molecular level. Here, we used reverse transcription PCR and Western blotting to analyze cultures of human gastric carcinoma cells exposed to 10 μM lead nitrate. We found that Pb2+ induces gastrin hormone gene transcription and translation in a time-dependent manner. Promoter deletion analysis revealed that activator protein 1 (AP1) was necessary for gastrin gene transcription in cells exposed to Pb2+. MitogIen-activated protein kinase (MAPK)/ERK kinase inhibitor PD98059 suppressed the Pb2+-induced increase in messenger RNA. Epidermal growth factor receptor (EGFR) inhibitors AG1478 and PD153035 reduced both transcription and phosphorylation by extracellular signal-regulated kinase (ERK1/2). Cells exposed to Pb2+ also increased production of c-Jun protein, a component of AP1, and over-expression of c-Jun enhanced activation of the gastrin promoter. In sum, the findings suggest the EGFR-ERK1/2-AP1 pathway mediates the effects of Pb2+ on gastrin gene activity in cell culture. © 2013 Wiley Periodicals, Inc. Environ Toxicol 30: 129–136, 2015.

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