Loss of EphA2 receptor tyrosine kinase reduces Apc Min/+ tumorigenesis

Christina Bogan, Jin Chen, Gerard O'Sullivan, Robert T Cormier

Research output: Contribution to journalArticlepeer-review

18 Scopus citations

Abstract

The Eph receptor A2 (EphA2) is overexpressed in a range of human epithelial cancers, a phenotype that is associated with cancer cell proliferation, progression and angiogenesis. Mouse models of mammary neoplasia have confirmed the role of EphA2 as mice carrying a knockout allele of EphA2 were resistant to breast cancer, a phenotype that was associated with interactions between EphA2 and ErbB2. We investigated in vivo the role of EphA2 in GI cancer. To determine whether EphA2 influences intestinal tumorigenesis, we used qRT-PCR to examine the mRNA expression levels, of EphA2 in tumors from the small intestine and colon of Apc Min/+ mice. We found that EpbA2 was significantly up-regulated in tumors from both regions when compared with normal control tissues. We then evaluated the spatial expression patterns of EphA2 protein using immunohistochemlstry in both the small intestine and colon and found that in normal tissues EphA2 was robustly expressed in highly differentiated cells, such as cells of the villi, but that Eph A 2 expression was largely absent from the stem cell niche and proliferative zones of intestinal crypts. In contrast, in tumors EphA2 was broadly expressed. Finally, we created a strain of Ape Min/+ mice carrying a genetic knockout of the EphA2 gene. These mice developed significantly fewer and smaller tumors in both the small and large intestine. Overall, our results indicate that EphA2 plays an oncogenic role in the mammalian intestine suggesting that strategies to target EphA2 activity may offer new therapeutic modalities for colorectal cancer.

Original languageEnglish (US)
Pages (from-to)1366-1371
Number of pages6
JournalInternational Journal of Cancer
Volume124
Issue number6
DOIs
StatePublished - Mar 15 2009

Keywords

  • Apc
  • Colon cancer
  • EphA2
  • Min
  • Receptor tyrosine kinase

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