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Article

Downregulation of epidermal growth factor receptor family receptors and ligands in a mutant K-ras group of patients with colorectal cancer

  • Authors:
    • Tomoko Nagaoka
    • Kazutaka Kitaura
    • Yukinaga Miyata
    • Kenichi Kumagai
    • Goro Kaneda
    • Hideki Kanazawa
    • Satsuki Suzuki
    • Yoshiki Hamada
    • Ryuji Suzuki
  • View Affiliations / Copyright

    Affiliations: Department of Oral and Maxillofacial Surgery, School of Dental Medicine, Tsurumi University, Tsurumi‑ku, Yokohama 230‑8501, Japan, Department of Rheumatology and Clinical Immunology, Clinical Research Center for Rheumatology and Allergy, Sagamihara National Hospital, National Hospital Organization, Sagamihara, Kanagawa 252‑0392, Japan, Department of Surgery, Sagamihara National Hospital, National Hospital Organization, Sagamihara, Kanagawa 252‑0392, Japan, Section of Biological Science, Research Center for Odontology, Nippon Dental University, School of Dentistry, Chiyoda‑ku, Tokyo 102‑0071, Japan
  • Pages: 3514-3520
    |
    Published online on: March 1, 2016
       https://doi.org/10.3892/mmr.2016.4951
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Abstract

The present study investigated the expression profiles of the epidermal growth factor receptor (EGFR) family, which consists of four transmembrane tyrosine kinase receptors and their eight ligands, in 122 patients with colorectal cancer (CRC) using reverse transcription-quantitative polymerase chain reaction analysis. On comparison of the CRC primary tumor and matched adjacent normal mucosa (ANM) tissue samples, the mRNA expression levels of ErbB3, but not ErbB1, were significantly increased in CRC tissue samples, compared with those in the ANM tissues. The expression levels of the ligands exhibited opposing trends to their corresponding receptors, including EGF, BTC, AREG, EREG and HB‑EGF, which were increased in the CRC tissues, whereas NRG1 and NGR2 were decreased in thee CRC tissues, compared with those in the AMN tissues. Subsequently, the present study investigated the frequency of K-ras mutations in the patients with CRC. The K‑ras mutations were found to be present in 36.8% (45/122) of the cases, however, no correlation was observed between K‑ras mutations and clinicopathological characteristics. In the CRC tissues, the expression levels of the EGFR family receptors and their ligands were determined in wild-type and mutant K-ras CRC cases. The expression levels of ErbB1, ErbB2, ErbB3, BTC, AREG, EREG, NRG1 and NRG2 were significantly decreased in the mutant K‑ras cases, compared with those in the wild‑type K‑ras cases. These results suggested that the tumorigenesis of CRC with wild‑type K‑ras was mediated through, not only ErbB1, but also through the ErbB2 and ErbB3 pathways. Notably, although ErbB2 does not bind any ErbB ligands, ErbB2 may activate tumorigenesis via a heterodimer, rather than a homodimer. Therefore, the results of the present study suggest that the most effective strategy to target not only ErbB1, but also ErbB2 and ErbB3, is the use of monoclonal antibody treatment.
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Copy and paste a formatted citation
Spandidos Publications style
Nagaoka T, Kitaura K, Miyata Y, Kumagai K, Kaneda G, Kanazawa H, Suzuki S, Hamada Y and Suzuki R: Downregulation of epidermal growth factor receptor family receptors and ligands in a mutant K-ras group of patients with colorectal cancer. Mol Med Rep 13: 3514-3520, 2016.
APA
Nagaoka, T., Kitaura, K., Miyata, Y., Kumagai, K., Kaneda, G., Kanazawa, H. ... Suzuki, R. (2016). Downregulation of epidermal growth factor receptor family receptors and ligands in a mutant K-ras group of patients with colorectal cancer. Molecular Medicine Reports, 13, 3514-3520. https://doi.org/10.3892/mmr.2016.4951
MLA
Nagaoka, T., Kitaura, K., Miyata, Y., Kumagai, K., Kaneda, G., Kanazawa, H., Suzuki, S., Hamada, Y., Suzuki, R."Downregulation of epidermal growth factor receptor family receptors and ligands in a mutant K-ras group of patients with colorectal cancer". Molecular Medicine Reports 13.4 (2016): 3514-3520.
Chicago
Nagaoka, T., Kitaura, K., Miyata, Y., Kumagai, K., Kaneda, G., Kanazawa, H., Suzuki, S., Hamada, Y., Suzuki, R."Downregulation of epidermal growth factor receptor family receptors and ligands in a mutant K-ras group of patients with colorectal cancer". Molecular Medicine Reports 13, no. 4 (2016): 3514-3520. https://doi.org/10.3892/mmr.2016.4951
Copy and paste a formatted citation
x
Spandidos Publications style
Nagaoka T, Kitaura K, Miyata Y, Kumagai K, Kaneda G, Kanazawa H, Suzuki S, Hamada Y and Suzuki R: Downregulation of epidermal growth factor receptor family receptors and ligands in a mutant K-ras group of patients with colorectal cancer. Mol Med Rep 13: 3514-3520, 2016.
APA
Nagaoka, T., Kitaura, K., Miyata, Y., Kumagai, K., Kaneda, G., Kanazawa, H. ... Suzuki, R. (2016). Downregulation of epidermal growth factor receptor family receptors and ligands in a mutant K-ras group of patients with colorectal cancer. Molecular Medicine Reports, 13, 3514-3520. https://doi.org/10.3892/mmr.2016.4951
MLA
Nagaoka, T., Kitaura, K., Miyata, Y., Kumagai, K., Kaneda, G., Kanazawa, H., Suzuki, S., Hamada, Y., Suzuki, R."Downregulation of epidermal growth factor receptor family receptors and ligands in a mutant K-ras group of patients with colorectal cancer". Molecular Medicine Reports 13.4 (2016): 3514-3520.
Chicago
Nagaoka, T., Kitaura, K., Miyata, Y., Kumagai, K., Kaneda, G., Kanazawa, H., Suzuki, S., Hamada, Y., Suzuki, R."Downregulation of epidermal growth factor receptor family receptors and ligands in a mutant K-ras group of patients with colorectal cancer". Molecular Medicine Reports 13, no. 4 (2016): 3514-3520. https://doi.org/10.3892/mmr.2016.4951
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