Skip to main page content
U.S. flag
See More

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2008 Oct 7;14(37):5650-6.
doi: 10.3748/wjg.14.5650.

Overexpression of the receptor tyrosine kinase EphA4 in human gastric cancers

Mariko Oki  1 , Hiroyuki Yamamoto, Hiroaki Taniguchi, Yasushi Adachi, Kohzoh Imai, Yasuhisa Shinomura
Affiliations

Overexpression of the receptor tyrosine kinase EphA4 in human gastric cancers

Mariko Oki et al. World J Gastroenterol. .

Abstract

Aim: To clarify the expression and role of Ephrin receptor A4 (EphA4) in gastric cancer in relation to clinicopathological characteristics and the expression of fibroblast growth factor receptor 1 (FGFR1) and ephrin ligands.

Methods: Eleven gastric carcinoma cell lines, 24 paired surgical fresh specimens of gastric adenocarcinoma and adjacent nontumor tissue, 74 conventional formalin-fixed, paraffin-embedded tumor specimens, and 55 specimens spotted on tissue microarray (TMA) were analyzed. Reverse transcription-PCR (RT-PCR), real-time RT-PCR, immunohistochemistry, and cell growth assays were performed.

Results: Overexpression of EphA4 mRNA expression was observed in 8 (73%) of 11 gastric cancer cell lines and 10 (42%) of 24 gastric cancer tissues. Overexpression of EphA4, analyzed by immunohistochemistry, was observed in 62 (48%) of 129 gastric cancer tissues. EphA4 overexpression, at the protein level, was significantly associated with depth of invasion and recurrence. EphA4 overexpression was also correlated with FGFR1 overexpression. Patients with EphA4-positive cancer had significantly shorter overall survival periods than did those with EphA4-negative cancer (P = 0.0008). The mRNAs for ephrin ligands were coexpressed in various combinations in gastric cancer cell lines and cancer tissues. Downregulation of EphA4 expression by siRNA in EphA4-overexpressing gastric cancer cell lines resulted in a significant decrease in cell growth.

Conclusion: Our results suggest that overexpression of EphA4 plays a role in gastric cancer.

PubMed Disclaimer

Figures

Figure 1
Figure 1
RT-PCR analysis of the EphA4 and FGFR1 in gastric cancer cell lines.
Figure 2
Figure 2
Real time RT-PCR (A) and semiquantitative RT-PCR (B) analysis of the EphA4 in gastric cancer tissues. A: From left to right; case 1 tumor, case 2 tumor, case 3 tumor, case 4 tumor, case 3 normal, case 1 normal, and case 2 normal; B: N and T = matched samples from non-tumor and tumor tissue, respectively.
Figure 3
Figure 3
Immunohistochemistry for EphA4 in gastric cancer tissues (× 200). A: Well differentiated gastric cancer negative for EphA4; B: Poorly differentiated gastric cancer negative for EphA4; C: Normal gastric epithelia negative for EphA4; D: Moderately differentiated gastric cancer positively stained for EphA4; E: Poorly differentiated gastric cancer positively stained for EphA4.
Figure 4
Figure 4
Kaplan-Meier survival curves of patients with gastric cancer according to the expression of EphA4 (P = 0.0008).
Figure 5
Figure 5
RT-PCR analysis of the type A ephrins and type B ephrins in gastric cancer cell lines. 1: NUGC3; 2: NUGC4; 3: SNU1; 4: SNU638; 5: MKN28; 6: MKN45; 7: MKN74; 8: KATOIII; 9: HGC27; 10: GC1Y; 11: AZ521.
See this image and copyright information in PMC

References

    1. Hamilton JP, Meltzer SJ. A review of the genomics of gastric cancer. Clin Gastroenterol Hepatol. 2006;4:416–425. - PubMed
    1. Tamura G. Alterations of tumor suppressor and tumor-related genes in the development and progression of gastric cancer. World J Gastroenterol. 2006;12:192–198. - PMC - PubMed
    1. Lin W, Kao HW, Robinson D, Kung HJ, Wu CW, Chen HC. Tyrosine kinases and gastric cancer. Oncogene. 2000;19:5680–5689. - PubMed
    1. Wu CW, Li AF, Chi CW, Huang CL, Shen KH, Liu WY, Lin W. Human gastric cancer kinase profile and prognostic significance of MKK4 kinase. Am J Pathol. 2000;156:2007–2015. - PMC - PubMed
    1. Kao HW, Chen HC, Wu CW, Lin WC. Tyrosine-kinase expression profiles in human gastric cancer cell lines and their modulations with retinoic acids. Br J Cancer. 2003;88:1058–1064. - PMC - PubMed

Publication types

MeSH terms