Fibroblast growth factor receptor 4 regulates proliferation and antiapoptosis during gastric cancer progression

Authors

  • Yan Wei Ye MD,

    1. Department of Abdominal Surgery, Fu Dan University Shanghai Cancer Center, Shanghai, China
    2. Department of Oncology, Shanghai Medical College, Fu Dan University, Shanghai, China
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  • Ye Zhou MD,

    1. Department of Abdominal Surgery, Fu Dan University Shanghai Cancer Center, Shanghai, China
    2. Department of Oncology, Shanghai Medical College, Fu Dan University, Shanghai, China
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  • Lin Yuan PhD,

    1. Department of Oncology, Shanghai Medical College, Fu Dan University, Shanghai, China
    2. Department of Pathology, Fu Dan University Shanghai Cancer Center, Shanghai, China
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  • Chun Meng Wang MD,

    1. Department of Abdominal Surgery, Fu Dan University Shanghai Cancer Center, Shanghai, China
    2. Department of Oncology, Shanghai Medical College, Fu Dan University, Shanghai, China
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  • Chun Yan Du MD,

    1. Department of Abdominal Surgery, Fu Dan University Shanghai Cancer Center, Shanghai, China
    2. Department of Oncology, Shanghai Medical College, Fu Dan University, Shanghai, China
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  • Xiao Yan Zhou MD,

    1. Department of Oncology, Shanghai Medical College, Fu Dan University, Shanghai, China
    2. Department of Pathology, Fu Dan University Shanghai Cancer Center, Shanghai, China
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  • Bi Qiang Zheng PhD,

    1. Department of Abdominal Surgery, Fu Dan University Shanghai Cancer Center, Shanghai, China
    2. Department of Oncology, Shanghai Medical College, Fu Dan University, Shanghai, China
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  • Xi Cao MD,

    1. Department of Abdominal Surgery, Fu Dan University Shanghai Cancer Center, Shanghai, China
    2. Department of Oncology, Shanghai Medical College, Fu Dan University, Shanghai, China
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  • Meng Hong Sun MD,

    1. Department of Oncology, Shanghai Medical College, Fu Dan University, Shanghai, China
    2. Department of Tissue Bank, Fu Dan University Shanghai Cancer Center, Shanghai, China
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  • Hong Fu MD,

    1. Department of Abdominal Surgery, Fu Dan University Shanghai Cancer Center, Shanghai, China
    2. Department of Oncology, Shanghai Medical College, Fu Dan University, Shanghai, China
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  • Ying Qiang Shi MD, PhD

    Corresponding author
    1. Department of Abdominal Surgery, Fu Dan University Shanghai Cancer Center, Shanghai, China
    2. Department of Oncology, Shanghai Medical College, Fu Dan University, Shanghai, China
    • Department of Abdominal Surgery, Fu Dan University Shanghai Cancer Center, 270 Dong-An Road, Shanghai 200032, China
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    • Fax: (011) 86-021-64174774


Abstract

BACKGROUND:

Fibroblast growth factor receptor 4 (FGFR4) belongs to the tyrosine kinase receptor family. Little is known about the effect of FGFR4 on gastric cancer (GC). Therefore, the objective of the current study was to elucidate the role of FGFR4 in the tumorigenesis and progression of GC.

METHODS:

FGFR4 and some common prognosis markers, including p53, neu, and proliferating cell nuclear antigen (PCNA), were detected in 71 tissue samples from patients with GC using immunohistochemical analysis. In addition, a series of functional assays were carried out using small interfering RNA (siRNA) and included proliferation assays, clone assays, and apoptosis detection.

RESULTS:

Cytoplasmic FGFR4 expression in GC tissues was negative (7% of samples), low (14.1% of samples), intermediate (40.8%), and high (38% of samples). FGFR4 expression was associated with lymph node status and with PCNA and neu expression (P < .05). The 5-year relative survival rate was 61.5% in patients who had GC with low FGFR4 expression but was only 42% in patients who had high FGFR4 expression (P = .058). A subgroup analysis of the patients who had high FGFR4 expression revealed that those with stage III and IV disease had a worse prognosis (P = .044). Moreover, knockdown of FGFR4 expression led to decreased proliferation and an increased rate of apoptosis in the MKN45 and SGC7901 GC cell lines (P < .05). Western blot analysis demonstrated that the expression of caspase 3 increased, whereas the expression of extra-large B-cell lymphoma (Bcl-xL) decreased in MKN45 and SGC7901 cells after FGFR4-siRNA transfection.

CONCLUSIONS:

FGFR4 expression in GC tissue was extremely high. The current results indicated that FGFR4 may contribute to the progression of GC by regulating proliferation and antiapoptosis, indicating that FGFR4 may be a potential, novel drug target against GC. Cancer 2011;. © 2011 American Cancer Society.

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