Skip to main page content
U.S. flag

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
. 2015 Apr;9(4):1672-1676.
doi: 10.3892/ol.2015.2925. Epub 2015 Feb 3.

Reduced expression of erythropoietin-producing hepatocyte B6 receptor tyrosine kinase in prostate cancer

Elnisr Rashed Mohamed  1 , Masanori Noguchi  2 , Ahmed Roshdi Hamed  3 , Mohamed Zaki Eldahshoury  1 , Ahmed Rashed Hammady  1 , Esam Elden Salem  1 , Kyogo Itoh  4
Affiliations

Reduced expression of erythropoietin-producing hepatocyte B6 receptor tyrosine kinase in prostate cancer

Elnisr Rashed Mohamed et al. Oncol Lett. 2015 Apr.

Abstract

Loss of erythropoietin-producing hepatocyte (Eph) B6 gene expression is associated with poor prognosis in neuroblastoma, melanoma and other tumors. The present study evaluated the expression of EphB6 receptor tyrosine kinase in normal and prostate cancer tissue using immunohistochemistry. The association between EphB6 expression, clinicopathological findings, proliferating-cell nuclear antigen (PCNA; another prognostic marker) and progression of prostate cancer was analyzed. Tissue microarray samples of normal prostatic tissue and prostate cancer tissue from 46 patients treated with radical prostatectomy for prostate cancer were included in this study. Polyclonal anti-EphB6 and monoclonal anti-PCNA antibodies were used to assess EphB6 and PCNA expression by immunohistochemistry. EphB6 was expressed in normal and prostate cancer tissue; however, its expression was significantly reduced in prostate cancer tissue compared with normal prostatic tissue (P<0.0001), in high volume (≥4 cm3) cancer compared with low volume (<4 cm3; P=0.015), and in pT3 stage compared with pT2 stage of the disease (P=0.0007). No correlation was observed between the expression of EphB6 and PCNA. Short biochemical progression-free survival was associated with low EphB6 protein expression (P=0.157). This study revealed that EphB6 may have a tumor suppressor effect in prostate cancer, at least during early stages of this disease. This provides new insight into the potential utility of EphB6 receptor as a diagnostic/prognostic marker for prostate cancer.

Keywords: biochemical progression-free survival; cancer volume; erythropoietin-producing hepatocyte B6 expression; prostate cancer; receptor tyrosine kinase.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Expression of EphB6 in normal and prostatic cancer tissue. Normal prostatic acini expressed EphB6 at either (A) moderate or (B) strong levels, while prostatic cancer tissue showed (C) negative, (D) weak, (E) moderate or (F) strong expression levels of EphB6. Magnification, ×400. Eph, erythropoietin-producing hepatocyte.
Figure 2
Figure 2
Expression of PCNA in prostate cancer tissue. Nuclear expression of PCNA with labeling index of (A) 18%, (B) 35% and (C) 85%. Magnification, ×400. PCNA, proliferating-cell nuclear antigen.
Figure 3
Figure 3
Association between tumor characteristics and EphB6 or PCNA expression. Association between EphB6 staining score and (A) Gleason score, (B) cancer volume and (C) pathological stage. Association between PCNA labeling index and (D) Gleason score, (E) cancer volume and (F) pathological stage. Eph, erythropoietin-producing hepatocyte; PCNA, proliferating-cell nuclear antigen; cc, cm3.
Figure 4
Figure 4
Kaplan-Meier plot showing time to biochemical progression-free survival of prostate cancer patients in different EphB6 expression groups. Eph, erythropoietin-producing hepatocyte.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Manning G, Whyte DB, Martinez R, et al. The protein kinase complement of the human genome. Science. 2002;298:1912–1934. doi: 10.1126/science.1075762. - DOI - PubMed
    1. Xu Q, Wilkinson DG. Eph-related receptors and their ligands: mediators of contact dependent cell interactions. J Mol Med (Berl) 1997;75:576–586. doi: 10.1007/s001090050142. - DOI - PubMed
    1. Nakamoto M. Eph receptors and ephrins. Int J Biochem Cell Biol. 2000;32:7–12. doi: 10.1016/S1357-2725(99)00096-5. - DOI - PubMed
    1. Holmberg J, Clarke DL, Frisén J. Regulation of repulsion versus adhesion by different splice forms of an Eph receptor. Nature. 2000;408:203–206. doi: 10.1038/35041577. - DOI - PubMed
    1. Kullander K, Klein R. Mechanisms and functions of Eph and ephrin signaling. Nat Rev Mol Cell Biol. 2002;3:475–486. doi: 10.1038/nrm856. - DOI - PubMed

LinkOut - more resources