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

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.

Differential Roles of Carboxylated and Uncarboxylated Osteocalcin in Prostate Cancer Growth

“…On the other hand, GlaOC also triggered increased phosphorylation of the same RTKs as GluOC, including FGFR1 12 , EphR 18 , ALK 19 , and RYK 20 . Additionally, GlaOC promoted the phosphorylation of additional nine RTKs, EphA10 15 , EphB4 17 , EphB6 27 , FGFR2a 28 , FGFR3 22 , DDR1 (discoidin domain receptor 1) 29 , VEGFR3 30 , Tie-2 31 , and TrkA 32 (Fig 2 B). The mechanisms for GluOC to promote the growth in normal cells, likely by activation of tyrosine kinases are currently unknown.…”

Cancer risk susceptibility loci in a Swedish population

“…The same gene has been suggested to harbor driver mutations in melanoma [ 22 ], and the Eph family receptors have been implicated in tumor progression and clinical outcome in several malignancies including tongue squamous cell-, ovarian-, gastric-, breast-, non-small cell lung cancer, melanoma and neuroblastoma [ 23 – 29 ]. The EphB6 has also been studied in thyroid-, and prostate cancer [ 30 , 31 ]. Up-regulation of the TRPV6 Ca 2+ channel in prostate cancer cells was suggested to promote cell proliferation rate, and to increase survival and apoptosis resistance in prostate cancer cells [ 32 ].…”

EPHB6 augments both development and drug sensitivity of triple-negative breast cancer tumours

“…Through their basal or ligand-induced signalling, kinase-active Eph receptors are frequently implicated in enhancing malignant behaviour of cancer cells [ 3 ] and in controlling tumour-initiating cells (TICs) [ 4 ]. In contrast, a strong negative correlation exists between the aggressiveness of solid tumours and kinase-dead EPHB6, with EPHB6 expression frequently reduced in aggressive malignancies, including invasive melanoma [ 5 ], metastatic lung and colorectal cancers [ 6 ], aggressive neuroblastoma [ 7 , 8 ], prostate, gastric and ovarian tumours [ 9 – 11 ]. EPHB6 also suppresses metastasis in xenograft models of human lung cancer [ 12 ], melanoma [ 13 ] and colorectal cancer [ 14 ], while our previous work indicates that it undergoes tyrosine phosphorylation in breast cancer cells and inhibits breast cancer invasiveness [ 15 ].…”