Phorbol ester phorbol-12-myristate-13-acetate induces epithelial to mesenchymal transition in human prostate cancer ARCaPE cells

Hui He, Alec J. Davidson, Daqing Wu, Fray F. Marshall, Leland W.K. Chung, Haiyen E. Zhau, Dalin He, Ruoxiang Wang

Research output: Contribution to journalArticle

20 Scopus citations

Abstract

BACKGROUND. We have reported that human prostate cancer ARCaPE cells undertake epithelial to mesenchymal transition (EMT) when stimulated by certain soluble factors, and that EMT is regulated by surface receptor-elicited signaling pathways through protein phosphorylation. It is known that phorbol ester phorbol-12-myristate-13-acetate (PMA), a potent antagonist to both conventional and novel protein kinase C (PKC) isoenzymes, induces cancer cell scattering. METHODS. To assess the effect of PMA on EMT, ARCaPE cells were treated with PMA and were assayed for EMT-related morphologic and behavioral changes. Specific inhibitors were used to investigate the PMA-induced EMT. RESULTS. PMA at 100nM induced EMT in a time-dependent manner, resulting in a complete change from epithelial to mesenchymal stromal morphology. Concurrently, PMA inhibited expression of epithelial marker E-cadherin and increased the level of stromal marker protein vimentin, while the treated cells showed increased migratory and invasive capacities. Using specific inhibitors, we confirmed that the effect of PMA was mediated by PKC, while isoenzymes of the novel PKC subfamily were implicated as the main mediator. Finally, we determined that the EMT was dependent on newly synthesized proteins, because inhibitors for gene transcription and protein translation could both inhibit the initiation of EMT. CONCLUSIONS. Although PMA is well known for its effects on cell migration and tumor formation, this work is the first to define PMA as an EMT inducer in prostate cancer cells. Further investigation in this experimental model may reveal important regulatory mechanisms and additional molecular changes underlying EMT.

Original languageEnglish (US)
Pages (from-to)1119-1126
Number of pages8
JournalProstate
Volume70
Issue number10
DOIs
StatePublished - Jul 1 2010

Keywords

  • Epithelial to mesenchymal transition
  • Metastasis
  • Phorbol-12-myristate-13-acetate
  • Prostate cancer progression
  • Protein kinase C

ASJC Scopus subject areas

  • Oncology
  • Urology

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    He, H., Davidson, A. J., Wu, D., Marshall, F. F., Chung, L. W. K., Zhau, H. E., He, D., & Wang, R. (2010). Phorbol ester phorbol-12-myristate-13-acetate induces epithelial to mesenchymal transition in human prostate cancer ARCaPE cells. Prostate, 70(10), 1119-1126. https://doi.org/10.1002/pros.21146