ERK5 signalling in prostate cancer promotes an invasive phenotype

AK Ramsay, SRC McCracken, M Soofi, J Fleming, AX Yu, I Ahmad, R Morland, L Machesky, C Nixon, DR Edwards, RR Nuttall, M Seywright, R Marquez, E Keller, HY Leung

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Abstract

Background: Aberrant mitogen/extracellular signal-regulated kinase 5 (MEK5)–extracellular signal-regulated protein kinase 5 (ERK5)-mediated signalling has been implicated in a number of tumour types including prostate cancer (PCa). The molecular basis of ERK5-driven carcinogenesis and its clinical relevance remain to be fully characterised. Methods: Modulation of ERK5 expression or function in human PCa PC3 and PC3–ERK5 (stably transfected with ERK5) cells was performed using siRNA-mediated knockdown or the MEK inhibitor PD18435 respectively. In vitro significance of ERK5 signalling was assessed by assays for proliferation, motility, invasion and invadopodia. Expression of matrix metalloproteinases/tissue inhibitors of metalloproteases was determined by Q-RT–PCR. Extracellular signal-regulated protein kinase 5 expression in primary and metastatic PCa was examined using immunohistochemistry. Results: Reduction of ERK5 expression or signalling significantly inhibited the motility and invasive capability of PC3 cells. Extracellular signal-regulated protein kinase 5-mediated signalling significantly promoted formation of in vivo metastasis in an orthotopic PCa model (P
Original languageEnglish
Pages (from-to)664-672
Number of pages9
JournalBritish Journal of Cancer
Volume104
Issue number4
DOIs
Publication statusPublished - 25 Jan 2011

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