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Role of Protein Kinase C Epsilon in Prostate Cancer and Metastasis

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Annual summary rept. 1 Jun 2011-31 Jul 2013

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The altered balance in the expression of PKC isozymes is a distinguished feature of cancer. One of the most notable alterations in epithelial cancers is the upregulation of PKC . This kinase has emerged as a potential oncogene and tumor biomarker, however, little is known regarding a potential causality between its upregulation and cancer development. In this research we wished to understand the role played by PKC in prostate cancer cells and establishes the proof of principle of PKC inhibition as a putative therapeutic strategy. We already found that PKC inhibition decreases size of tumor generated by PC3-ML cells in athymicbalb-c mice. Therefore, during this second year we have focus in the study of the metastasic properties of PKCe. Using an RNAi approach we found that PKC depletion markedly impaired the ability of PC3-ML metastasize in bone marrow of athymicbalb-c mice. In addition we found that this kinase is relevant in attachment, MMPs activity, cytokines expression, and anchorage-dependent and anchorage- independent growth of PC3-ML cells. Moreover, we have determined that pharmacological inhibition of PKCe significantly reduced invasiveness phenotype of PC3-ML. In summary, our results argue for a role of PKC in prostate cancer development and metastasis, highlighting its potential as a therapeutic target.

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  • Biochemistry
  • Medicine and Medical Research

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