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Original article| Volume 141, ISSUE 5, P335-341, May 2003

Oncogenic ras induces gastrin/CCKB receptor gene expression in human colon cancer cell lines LoVo and Colo320HSR

  • Hiroyuki Hori
    Affiliations
    Department of Biosignal Pathophysiology, Graduate School of Medicine and Medical Center for Student Health, Kobe, Japan
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  • Hirohisa Nakata
    Correspondence
    Reprint requests: Hirohisa Nakata, MD, Department of Biosignal Pathophysiology, Kobe University Graduate School of Medicine, 1-1 Rokkodai-cho, Nada-ku, Kobe 657-8501, Japan.
    Affiliations
    Department of Biosignal Pathophysiology, Graduate School of Medicine and Medical Center for Student Health, Kobe, Japan
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  • Genzo Iguchi
    Affiliations
    Division of Endocrinology/Metabolism, Neurology, and Hematology/Oncology, Department of Clinical Molecular Medicine, Graduate School of Medicine, Kobe University, Kobe, Japan
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  • Hajime Yamada
    Affiliations
    Division of Endocrinology/Metabolism, Neurology, and Hematology/Oncology, Department of Clinical Molecular Medicine, Graduate School of Medicine, Kobe University, Kobe, Japan
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  • Kazuo Chihara
    Affiliations
    Division of Endocrinology/Metabolism, Neurology, and Hematology/Oncology, Department of Clinical Molecular Medicine, Graduate School of Medicine, Kobe University, Kobe, Japan
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  • Hisamitsu Baba
    Affiliations
    Department of Biosignal Pathophysiology, Graduate School of Medicine and Medical Center for Student Health, Kobe, Japan
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      Abstract

      Gastrin has the ability to stimulate cell growth in some colorectal cancer cells and some of these cells also express gastrin/CCKB receptors, suggesting that gastrin and its autocrine loop are involved in their proliferation. We previously reported that oncogenic ras induced gastrin gene expression in colon cancer cells. The aim of this study was to investigate whether oncogenic ras also induces gastrin/CCKB receptor gene expression. A transiently transfected activated ras vector stimulated gastrin/CCKB receptor transcriptional activities in both Colo320HSR and LoVo cells, but these ras-increased activities were inhibited by a specific MEK inhibitor, PD98059. An RPA demonstrated that activated ras increased endogenous gastrin/CCKB receptor mRNA levels and PD98059 decreased them in LoVo cells. These findings suggest that oncogenic ras induces gastrin/CCKB receptor gene expression through some intracellular signaling pathways, including MEK, in colon cancer cell lines.

      Keywords:

      APC (adenomatous polyposis coli), bp (base pair), CCKB (cholecystokinin B), DMSO (dimethylsulfoxide), EDTA (ethylenediaminetetraacetic acid), ERK (extracellular signal–regulated kinase), FCS (fetal calf serum), GAPDH (glyceraldehyde phosphate dehydrogenase), gly-gastrin (glycine-extended gastrin), MAPK (mitogen-activated protein kinase), MEK (MAPK/ERK kinase), mRNA (messenger RNA), RLU (relative light unit), RPA (ribonuclease-protection assay), RT-PCR (reverse transcription–polymerase chain reaction), SDS (sodium dodecyl sulfate), SEM (standard error of the mean), TCF-4 (T-cell factor-4)
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