Abstract | BACKGROUND: METHODS: We employed transient knockdown of EPHB4 in prostate cancer cells, coupled with gene microarray analysis, to identify genes that were regulated by EPHB4 and may represent linked tumor-promoting factors. We validated target genes using qRT-PCR and employed functional assays to determine their role in prostate cancer migration and invasion. RESULTS: We discovered that over 500 genes were deregulated upon EPHB4 siRNA knockdown, with integrin β8 (ITGB8) being the top hit (29-fold down-regulated compared to negative non-silencing siRNA). Gene ontology analysis found that the process of cell adhesion was highly deregulated and two other integrin genes, ITGA3 and ITGA10, were also differentially expressed. In parallel, we also discovered that over-expression of EPHB4 led to a concomitant increase in ITGB8 expression. In silico analysis of a prostate cancer progression microarray publically available in the Oncomine database showed that both EPHB4 and ITGB8 are highly expressed in prostatic intraepithelial neoplasia, the precursor to prostate cancer. Knockdown of ITGB8 in PC-3 and 22Rv1 prostate cancer cells in vitro resulted in significant reduction of cell migration and invasion. CONCLUSIONS:
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Authors | Inga Mertens-Walker, Bruno C Fernandini, Mohanan S N Maharaj, Anja Rockstroh, Colleen C Nelson, Adrian C Herington, Sally-Anne Stephenson |
Journal | BMC cancer
(BMC Cancer)
Vol. 15
Pg. 164
(Mar 22 2015)
ISSN: 1471-2407 [Electronic] England |
PMID | 25886373
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Integrin beta Chains
- integrin beta8
- Receptor Protein-Tyrosine Kinases
- Receptor, EphB4
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Topics |
- Cell Line, Tumor
- Gene Expression Regulation, Neoplastic
- Humans
- Integrin beta Chains
(biosynthesis)
- Male
- Prostatic Neoplasms
(metabolism, pathology)
- Receptor Protein-Tyrosine Kinases
(physiology)
- Receptor, EphB4
(physiology)
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