Complex expression patterns of Eph receptor tyrosine kinases and their ephrin ligands in colorectal carcinogenesis

Herath, Nirmitha I., Spanevello, Mark D., Doecke, James D., Smith, Fiona M., Pouponnot, Celio and Boyd, Andrew W. (2012) Complex expression patterns of Eph receptor tyrosine kinases and their ephrin ligands in colorectal carcinogenesis. European Journal of Cancer, 48 5: 753-762. doi:10.1016/j.ejca.2011.07.003


Author Herath, Nirmitha I.
Spanevello, Mark D.
Doecke, James D.
Smith, Fiona M.
Pouponnot, Celio
Boyd, Andrew W.
Title Complex expression patterns of Eph receptor tyrosine kinases and their ephrin ligands in colorectal carcinogenesis
Journal name European Journal of Cancer   Check publisher's open access policy
ISSN 0959-8049
1879-0852
Publication date 2012-03
Year available 2011
Sub-type Article (original research)
DOI 10.1016/j.ejca.2011.07.003
Volume 48
Issue 5
Start page 753
End page 762
Total pages 10
Place of publication Oxford, United Kingdom
Publisher Pergamon
Collection year 2012
Language eng
Abstract Aberrant expression of Eph and ephrin proteins in human cancers is extensively documented. However, data are frequently limited to one gene and therefore incomplete and in some instances conflicting. We analysed expression of all Eph and ephrin genes in colorectal cancer (CRC) cell lines and 153 clinical specimens, providing for the first time a comprehensive analysis of this system in CRC. Eph/ephrin mRNA expression was assessed by quantitative real-time PCR and correlated with protein expression (flow cytometry, Western blotting and immunocytochemistry). These data show that EphA1, EphA2, EphB2 and EphB4 were significantly over expressed in CRC. In all cases, at least one Eph gene was found in normal colon (EphA1, EphA2, EphB2, EphB4), where expression was observed at high levels in most CRCs. However, other Eph gene expression was lost in individual CRCs compared to the corresponding normal, EphA7 being a striking example. Loss of expression was more common in advanced disease and thus correlated with poor survival. This is consistent with the redundant functionality of Eph receptors, such that expression of a single Eph gene is sufficient for effector function. Overall, the data suggest a progressive loss of expression of individual Eph genes suggesting that individual CRCs need to be phenotyped to determine which Eph genes are highly expressed. Targeted therapies could then be selected from a group of specific antibodies, such as those developed for EphA1.
Keyword Colorectal carcinogenesis
Eph receptors
Ephrin ligands
Q-Pcr
Antibodies
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ
Additional Notes Available online 16 August 2011.

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2012 Collection
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